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https://www.readbyqxmd.com/read/29672662/fibrostenotic-phenotype-of-myofibroblasts-in-crohn-s-disease-is-dependent-on-tissue-stiffness-and-reversed-by-lox-inhibition
#1
Jessica R de Bruyn, Gijs R van den Brink, Jessica Steenkamer, Christianne J Buskens, Willem A Bemelman, Sander Meisner, Vanesa Muncan, Anje A Te Velde, Geert R D'Haens, Manon E Wildenberg
Background and Aims: Crohn's disease is a chronic inflammatory disorder of the intestine and often leads to fibrosis, characterized by excess extracellular matrix [ECM] deposition, increased tissue stiffness, and stricture formation. Here we evaluated the contribution of myofibroblast-ECM interactions to the development of intestinal fibrosis in Crohn's disease. Methods: Matched primary human myofibroblasts were isolated from stenotic, inflamed and normal-appearing small intestine within the same Crohn's disease patient [n = 10]...
April 16, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29667908/the-macula-densa-prorenin-receptor-is-essential-in-renin-release-and-blood-pressure-control
#2
Anne D M Riquier-Brison, Arnold Sipos, Ágnes Prókai, Sarah L Vargas, Ildiko Toma, Elliott J Meer, Karie G Villanueva, Jennifer C M Chen, Georgina Gyarmati, Christopher Yih, Elaine Tang, Bahram Nadim, Sujith Pendekanti, Ingrid M Garrelds, Genevieve Nguyen, A H Jan Danser, Janos Peti-Peterdi
The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS), however recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29664544/human-skin-model-for-mimic-dermal-studies-in-pathology-with-a-clinical-implication-in-pressure-ulcers
#3
Lara Cristóbal, Miguel A Ortega, Ángel Asúnsolo, Beatriz Romero, Melchor Álvarez-Mon, Julia Buján, Andrés A Maldonado, Natalio García-Honduvilla
Despite advances in regenerative medicine and tissue engineering, human skin substitutes remain a clear goal to achieve. Autografts remain the principal clinical option. The long-term changes in dermis, as well as its response after injuries, are not well known. Research in this field has been hindered by a lack of experimental animal models. This study analyzes the architectural dermal scaffold (collagen and elastin fibers plus fibrillin-microfibrils) changes in a model of human skin pressure ulcers in mice...
April 17, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29662563/-123-i-labeled-oxldl-is-widely-distributed-throughout-the-whole-body-in-mice
#4
Atushi Nakano, Hidekazu Kawashima, Yoshinori Miyake, Tsutomu Zeniya, Akihide Yamamoto, Kazuhiro Koshino, Takashi Temma, Tetsuya Fukuda, Yoshiko Fujita, Akemi Kakino, Shigehiko Kanaya, Tatsuya Sawamura, Hidehiro Iida
Purpose: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice. Methods: We synthesized 123 I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the 123 I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver...
April 2018: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29661738/overexpression-of-lox-in-triple-negative-breast-cancer
#5
Cornelia Leo, Christine Cotic, Victoria Pomp, Daniel Fink, Zsuzsanna Varga
BACKGROUND: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the expression of estrogen and progesterone receptors and Her2 status is also negative, there is currently no target that can be used for systemic therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor progression and metastasis...
March 27, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29660236/oxylipins-from-both-pathogen-and-host-antagonize-ja-mediated-defense-via-the-9-lipoxygenase-pathway-in-fusarium-vertcillioides-infection-of-maize
#6
Paola Battilani, Alessandra Lanubile, Valeria Scala, Massimo Reverberi, Rossella Gregori, Claudia Falavigna, Chiara Dall'Asta, Yong-Soon Park, John Bennett, Eli J Borrego, Michael V Kolomiets
Oxylipins are a newly emerging group of signals that serve either defense roles or promote virulence. To identify specific host and fungal genes and oxylipins governing the interactions between maize and Fusarium verticillioides, maize wild-type and lipoxygenase3 (lox3) mutant were inoculated with either F. verticillioides wild-type or linoleate-diol-synthase 1-deleted mutant (ΔFvlds1D). Results showed that lox3 mutants were more resistant to F. verticillioides. The reduced colonization on lox3 was associated with reduced fumonisin production and with a stronger and earlier induction of ZmLOX4, ZmLOX5, and ZmLOX12...
April 16, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29658436/thrombin-alters-human-endometrial-stromal-cell-differentiation-during-decidualization
#7
Samir N Babayev, Mohammed Kanchwala, Chao Xing, Yucel Akgul, Bruce R Carr, Ruth Ann Word
Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor ( IGF)-1, Insulin-like growth factor binding protein ( IGFBP)-1, and PRL gene expression at baseline and during decidualization...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29651867/molecular-modelling-insights-into-a-physiologically-favourable-approach-to-eicosanoid-biosynthesis-inhibition-through-novel-thieno-2-3-b-pyridine-derivatives
#8
Mosaad S Mohamed, Yara E Mansour, Hatem K Amin, Moustafa E El-Araby
In this research, we exploited derivatives of thieno[2,3-b]pyridine as dual inhibitors of the key enzymes in eicosanoid biosynthesis, cyclooxygenase (COX, subtypes 1 and 2) and 5-lipoxygensase (5-LOX). Testing these compounds in a rat paw oedema model revealed potency higher than ibuprofen. The most active compounds 7a, 7b, 8b, and 8c were screened against COX-1/2 and 5-LOX enzymes. Compound 7a was the most powerful inhibitor of 5-LOX with IC50  = 0.15 µM, while its p-chloro analogue 7b was more active against COX-2 (IC50  = 7...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29650694/lymphatic-vasculature-requires-er-estrogen-receptor-%C3%AE-signaling-to-protect-from-lymphedema
#9
Florent Morfoisse, Florence Tatin, Benoit Chapût, Nicole Therville, Charlotte Vaysse, Raphael Métivier, Julie Malloizel-Delaunay, Francoise Pujol, Anne-Claire Godet, Fabienne De Toni, Frederic Boudou, Katia Grenier, David Dubuc, Eric Lacazette, Anne-Catherine Prats, Julie Guillermet-Guibert, Francoise Lenfant, Barbara Garmy-Susini
OBJECTIVE: Estrogens exert beneficial effect on the blood vascular system. However, their role on the lymphatic system has been poorly investigated. We studied the protective effect of the 17β estradiol-the most potent endogenous estrogen-in lymphedema-a lymphatic dysfunction, which results in a massive fluid and fat accumulation in the limb. APPROACH AND RESULTS: Screening of DNA motifs able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional activation of lymphangiogenesis-related gene expression including VEGF (vascular endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs (hyaluronan synthases)...
April 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29627380/12-15-lipoxygenase-a-crucial-enzyme-in-diverse-types-of-cell-death
#10
REVIEW
Qiu-Qi Li, Qin-Li, Ji-Ning Jia, Zhao-Qian Liu, Hong-Hao Zhou, Xiao-Yuan Mao
The 12/15-lipoxygenase (12/15-LOX) enzymes react with polyunsaturated fatty acids producing active lipid metabolites that are involved in plethora of human diseases including neurological disorders. A great many of elegant studies over the last decades have contributed to unraveling the mechanism how 12/15-lipoxygenase play a role in these diseases. And the way it works is mainly through apoptosis. However, recent years have found that the way 12/15-lipoxygenase works is also related to autophagy and ferroptosis, a newly defined type of cell death by Stockwell's lab in 2012...
April 5, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29627371/the-apparent-competitive-action-of-ecm-proteases-and-cross-linking-enzymes-during-fibrosis-applications-to-drug-discovery
#11
Nikolaos A Afratis, Mordehay Klepfish, Nikos K Karamanos, Irit Sagi
Progressive loss of organ function in most organs is associated with fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death. Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts...
April 5, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29624122/docking-steered-molecular-dynamics-and-qsar-studies-as-strategies-for-studying-isoflavonoids-as-5-12-and-15-lipoxygenase-inhibitors
#12
Francisco Cabezas, Carolina Mascayano
Lipoxygenases (LOX) are enzymes that catalyze polyunsaturated fatty acid peroxidation and have a non-heme iron atom located in their active site. They are implicated in the arachidonic acid pathway and involved in inflammation, fever, pain production and in the origins of several diseases such as cancer, asthma and psoriasis. The search for inhibitors of these enzymes has emerged in the last years, and isoflavonoids have a broad spectrum of biological activity with low cytotoxicity. Our previous results have shown that isoflavonoids inhibited different LOX isoforms in vitro...
April 6, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29620941/cerebrovascular-%C3%AE-amyloid-deposition-and-associated-microhemorrhages-in-a-tg2576-alzheimer-mouse-model-are-reduced-with-a-dha-enriched-diet
#13
Justine Hur, Véronique Mateo, Nicolas Amalric, Mégane Babiak, Gilbert Béréziat, Claire Kanony-Truc, Thierry Clerc, Régis Blaise, Isabelle Limon
Cerebral amyloid angiopathy (CAA) is a major contributor to Alzheimer's disease (AD) pathogenesis. Like AD, CAA is often accompanied by marked inflammation, aggravating associated vasculopathies. No evidence-based prevention or treatment strategies are available. Here, we evaluate the possible beneficial effect of a diet enriched with docosahexaenoic acid (DHA), which is known to attenuate inflammation in CAA. Tg2576 mice, a transgenic model of AD/CAA, were fed a DHA-enriched diet starting at 2 mo of age and ending at 10, 14, or 18 mo of age...
April 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29619884/cardioprotective-effect-of-%C3%AE-d-mannuronic-acid-m2000-as-a-novel-nsaid-on-gene-expression-of-oxldl-scavenger-receptors-in-the-experimental-diabetic-model
#14
Seyed Shahabeddin Mortazavi-Jahromi, Shahab Alizadeh, Mohammad Hassan Javanbakht, Abbas Mirshafiey
CONTEXT: The investigations have shown that patients with diabetes have the elevated levels of glucose and oxLDL. These two play an important role in increased expression levels of oxLDL scavenger receptors on the surface of macrophages and endothelial cells that leads to deposition of oxLDL and macrophages in vascular walls. OBJECTIVE: The present study intends to show the effects of β-d-mannuronic acid (M2000) on the expression profile of ox-LDL scavenger receptors (including SR-A, LOX-1, CD36, and CD68) in an experimental model of diabetes...
April 5, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29617722/pcsk9-regulates-expression-of-scavenger-receptors-and-ox-ldl-uptake-in-macrophages
#15
Zufeng Ding, Shijie Liu, Xianwei Wang, Sue Theus, Xiaoyan Deng, Yubo Fan, Sichang Zhou, Jawahar L Mehta
Aims: PCSK9 has been shown to influence macrophage biology and modulate atherogenesis. We conducted this study to examine the regulation of scavenger receptors (SRs) (LOX-1, SRA and CD36) and oxidized liporoptein cholesterol (ox-LDL) uptake in macrophages by PCSK9. Methods and Results: Treatment of mouse peritoneal macrophages with TNF-α resulted in concentration-dependent modest, but significant, increase in PCSK9 expression. Importantly, treatment of TNF-α primed macrophages with recombinant murine PCSK9 increased the expression of LOX-1, SRA and CD36 2-5 fold, and enhanced ox-LDL uptake by ≈5-fold...
March 29, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29617044/pcsk9-plays-a-novel-immunological-role-in-the-oxidized-ldl-induced-dendritic-cell-maturation-and-t-cell-activation-from-human-blood-and-atherosclerotic-plaque
#16
Anquan Liu, Johan Frostegård
BACKGROUND: Activated T cells and dendritic cells (DCs) occur in atherosclerotic plaques. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR), and results in increased LDL-levels. We here investigate immune effects of PCSK9 on OxLDL induced DC maturation and T cell activation. METHODS: T cells were isolated from carotid specimens of patients undergoing carotid endarterectomy, or from peripheral blood of healthy individuals. Human peripheral blood monocytes were differentiated into DCs...
April 4, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29615815/cardiac-myo-fibroblasts-modulate-the-migration-of-monocyte-subsets
#17
Kathleen Pappritz, Konstantinos Savvatis, Annika Koschel, Kapka Miteva, Carsten Tschöpe, Sophie Van Linthout
Cardiac fibroblasts play an important role in the regulation of the extracellular matrix and are newly recognized as inflammatory supporter cells. Interferon (IFN)-γ is known to counteract transforming growth factor (TGF)-ß1-induced myofibroblast differentiation. This study aims at investigating in vitro how IFN-γ affects TGF-ß1-induced monocyte attraction. Therefore, C4 fibroblasts and fibroblasts obtained by outgrowth culture from the left ventricle (LV) of male C57BL6/j mice were stimulated with TGF-β1, IFN-γ and TGF-β1 + IFN-γ...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615467/late-neuroprogenitors-contribute-to-normal-retinal-vascular-development-in-a-hif2a-dependent-manner
#18
Enrico Cristante, Sidath E Liyanage, Robert D Sampson, Aikaterini Kalargyrou, Giulia De Rossi, Matteo Rizzi, Justin Hoke, Joana Ribeiro, Ryea N Maswood, Yanai Duran, Takaaki Matsuki, Nozie Aghaizu, Ulrich F Luhmann, Alexander J Smith, Robin R Ali, James W B Bainbridge
In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of their critical relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a ( Hif2a )...
April 3, 2018: Development
https://www.readbyqxmd.com/read/29611204/evidence-for-the-anti-inflammatory-activity-of-bupleurum-marginatum-apiaceae-extracts-using-in-vitro-and-in-vivo-experiments-supported-by-virtual-screening
#19
Mohamed L Ashour, Fadia S Youssef, Haidy A Gad, Mahmoud Z El-Readi, Amel Bouzabata, Riham M Abuzeid, Mansour Sobeh, Michael Wink
OBJECTIVES: To explore the potential anti-inflammatory activity of Bupleurum marginatum extracts using in vitro and in vivo studies supported by virtual screening. METHODS: Antioxidant activity was assessed using the DPPH˙ and inhibition of 2-deoxyribose degradation assays. Anti-inflammatory activity was determined in vitro by measuring the suppression of prostaglandin E2 release (PGE2 ) in pancreatic cancer cells (MIA-PaCa-2) and the inhibition of 5-lipoxygenase whereas the rat paw oedema was used in vivo...
April 3, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29611071/study-of-defense-related-gene-expression-in-grapevine-infested-by-colomerus-vitis-acari-eriophyidae
#20
Saeid Javadi Khederi, Mohammad Khanjani, Mansur Gholami, Giovanni Luigi Bruno
Real-time quantitative polymerase chain reaction was used to study the expression of some marker genes involved in the interaction between grape (Vitis vinifera L.) and the erineum mite Colomerus vitis Pagenstecher (Acari: Eriophyidae). Potted vines of cultivars Atabaki (resistant to C. vitis), Ghalati (susceptible to C. vitis) and Muscat Gordo (moderately resistant to C. vitis) were infested at the six-leaf stage. The expression of protease inhibitor (PIN), beta-1,3-glucanase (GLU), polygalacturonase inhibitor (PGIP), Vitis vinifera proline-rich protein 1 (PRP1), stilbene synthase (STS), and lipoxygenase (LOX) genes was assessed on young leaves collected 96, 120 and 144 h after mite infestation (hami)...
April 2, 2018: Experimental & Applied Acarology
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