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https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#1
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#2
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27908549/noni-leaf-and-black-tea-enhance-bone-regeneration-in-estrogen-deficient-rats
#3
Nor Aijratul Asikin Mohd Shalan, Noordin M Mustapha, Suhaila Mohamed
OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats. METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh)...
January 2017: Nutrition
https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#4
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#5
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904582/the-role-of-peroxisome-proliferator-activated-receptor-coactivator-1-gene-in-skin-aging
#6
REVIEW
Shahrzad Aghaei, Mohammad Ali Nilforoushzadeh, Maryam Aghaei
Skin aging is a continuous process that exhibits fine and deep wrinkles, thin and transparent skin, loss of underlying fat, dry skin and itch, following decreased collagen and elastin synthesis. Both extrinsic and intrinsic agents are considered in the pathogenesis on skin aging. Extrinsic factors such as sun exposure, windy and dry weather, nutrition, and lifestyle may induce premature aging, toxic-free radicals, and reactive oxygen species due to decreasing normal function of mitochondria which play the major intrinsic factors in premature skin aging...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903864/oral-thrombin-inhibitor-aggravates-platelet-adhesion-and-aggregation-during-arterial-thrombosis
#7
Tobias Petzold, Manuela Thienel, Ildiko Konrad, Irene Schubert, Ron Regenauer, Boj Hoppe, Michael Lorenz, Annekathrin Eckart, Sue Chandraratne, Carsten Lennerz, Christof Kolb, Daniel Braun, Janina Jamasbi, Richard Brandl, Siegmund Braun, Wolfgang Siess, Christian Schulz, Steffen Massberg
In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903449/sex-differences-in-the-estrogen-dependent-regulation-of-temporomandibular-joint-remodeling-in-altered-loading
#8
Jennifer L Robinson, Katelyn Cass, Ross Aronson, Thomas Choi, Manshan Xu, Ryan Buttenbaum, Hicham Drissi, Helen H Lu, Jing Chen, Sunil Wadhwa
OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERβ) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERβ signaling in mediating DOL effects in male mice to further decipher sex differences...
November 26, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27899232/expression-of-muscarinic-acetylcholine-receptors-in-hepatocytes-from-rat-fibrotic-liver
#9
Lin Luo, Tingting Xu, Pengbo Wang, Liuliu Mao, Chenghao Xi, Jinhua Huang, Wei Zhang
The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated...
November 26, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27898753/-oncogen-dependent-regulation-of-the-migration-and-proliferation-of-human-tumor-cells
#10
Tamás M Garay
The high mortality of solid tumors can be attributed to their invasive and metastatic potential that is based on their migration and proliferation. Importantly, growth factor receptor (GF) signaling pathways regulating proliferation and migration are often affected by oncogenic mutations and are important targets for antitumor therapy. We found positive correlation between migration and proliferation in melanoma and lung cancer cells using videomicroscopy, not supporting the "go or grow" hypothesis. Furthermore, the invasion into collagen I matrices from brain tumor spheroids was not impaired upon the inhibition of proliferation...
November 29, 2016: Magyar Onkologia
https://www.readbyqxmd.com/read/27894619/expression-of-pro-fibrotic-and-anti-fibrotic-molecules-in-dimethylnitrosamine-induced-hepatic-fibrosis
#11
Roberta Sferra, Antonella Vetuschi, Simona Pompili, Eugenio Gaudio, Silvia Speca, Giovanni Latella
BACKGROUND: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors. OBJECTIVE: To evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice...
November 11, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27894386/-study-of-the-correlation-between-the-expression-of-angiotensin-%C3%A2-and-its-receptors-and-collagen-deposition-in-human-keloid
#12
J J Chen, X J Wu, Z Y Zhang, Z X Chen, Y Cen
Objective: To study the correlation between the expression of angiotensin Ⅱ, angiotensin Ⅱ type 1 receptor (AT1R), angiotensin Ⅱ type 2 receptor (AT2R) and collagen deposition in human keloid. Methods: The keloid from 19 keloid patients and normal skin from 13 patients performed with free skin transplantation hospitalized in our unit from May 2014 to January 2015 were obtained. The expressions of angiotensin Ⅱ, AT1R, and AT2R were detected by immunohistochemical staining, and the results were semi-quantitatively analyzed by immunohistochemical scoring...
November 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27894125/intronic-polyadenylation-of-pdgfr%C3%AE-in-resident-stem-cells-attenuates-muscle-fibrosis
#13
Alisa A Mueller, Cindy T van Velthoven, Kathryn D Fukumoto, Tom H Cheung, Thomas A Rando
Platelet-derived growth factor receptor α (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle. However, both increased PDGF ligand abundance and enhanced PDGFRα pathway activity cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders...
November 28, 2016: Nature
https://www.readbyqxmd.com/read/27893751/25-hydroxy-and-1%C3%AE-25-dihydroxycholecalciferol-have-greater-potencies-than-25-hydroxy-and-1%C3%AE-25-dihydroxyergocalciferol-in-modulating-cultured-human-and-mouse-osteoblast-activities
#14
Allahdad Zarei, Philippa A Hulley, Afsie Sabokbar, M Kassim Javaid, Alireza Morovat
Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts...
2016: PloS One
https://www.readbyqxmd.com/read/27889505/candesartan-ameliorates-arsenic-induced-hypertensive-vascular-remodeling-by-regularizing-angiotensin-ii-and-tgf-beta-signaling-in-rats
#15
Maibam Wanta Khuman, Sankaran Kutty Harikumar, Abdul Sadam, Manickam Kesavan, Vattaparambil Sukumaran Susanth, Subhashree Parida, Karam Pal Singh, Souvendra Nath Sarkar
Arsenic exposure can cause several cardiovascular diseases, including hypertension, atherosclerosis and microvascular disease. Earlier, we reported that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair vascular physiology. Here, we investigated whether the AT1 receptor (AT1R) blocker candesartan can ameliorate the arsenic-induced hypertensive vascular remodeling in rats and whether the amelioration could relate to attenuation in vascular AngII and TGF-β signaling. Rats were exposed to sodium arsenite (50ppm) through drinking water for 90 consecutive days...
November 23, 2016: Toxicology
https://www.readbyqxmd.com/read/27886093/hmgb1-promotes-intraoral-palatal-wound-healing-through-rage-dependent-mechanisms
#16
Salunya Tancharoen, Satoshi Gando, Shrestha Binita, Tomoka Nagasato, Kiyoshi Kikuchi, Yuko Nawa, Pornpen Dararat, Mika Yamamoto, Somphong Narkpinit, Ikuro Maruyama
High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 (Hmgb1(+/-)) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies...
November 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27885904/the-effect-of-p2y12-inhibition-on-platelet-activation-assessed-with-aggregation-and-flow-cytometry-based-assays
#17
Tesse C Leunissen, Peter Paul Wisman, Thijs C van Holten, Philip G de Groot, Suzanne J Korporaal, Arnold C Koekman, Frans L Moll, Martin Teraa, Marianne C Verhaar, Gert Jan de Borst, Rolf T Urbanus, Mark Roest
Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo...
November 25, 2016: Platelets
https://www.readbyqxmd.com/read/27885847/receptor-specific-trail-as-a-means-to-achieve-targeted-elimination-of-activated
#18
Mohammad Arabpour, Robbert Cool, Klaas Nico Faber, Wim J Quax, Hidde J Haisma
Activated Hepatic Stellate Cells (HSCs) are known to play a central role in liver fibrosis and their elimination is a crucial step towards the resolution and reversion of liver fibrosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a molecule that may contribute to the apoptotic removal of activated HSC through binding to its dedicated receptors. In the present study, we investigated the potential application of recombinant receptor-specific TRAIL proteins in the efficient elimination of activated HSCs...
November 25, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#19
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27884442/the-induction-of-the-collagen-capsule-synthesis-by-trichinella-spiralis-is-closely-related-to-protease-activated-receptor-2
#20
Mi Kyung Park, Min Kyoung Cho, Shin Ae Kang, Bo Young Kim, Hak Sun Yu
The muscle-stage larvae of the parasite Trichinella spiralis have the ability to survive within host muscle tissue by virtue of the formation a nurse cell-parasite complex, which is surrounded by collagen. The formation of the complex is initiated by excretory-secretory (ES) proteins produced by the parasite. To determine the mechanisms underlying collagen capsule formation, we investigated the expression levels of several types of collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) in muscle cells...
October 30, 2016: Veterinary Parasitology
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