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https://www.readbyqxmd.com/read/28641286/effect-of-bexarotene-on-platelet-activation-and-apoptosis
#1
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28636167/berberine-ameliorates-collagen-induced-arthritis-in-rats-by-suppressing-th17-cell-responses-via-inducing-cortistatin-in-the-gut
#2
Mengfan Yue, Yufeng Xia, Can Shi, Chunge Guan, Yunfan Li, Rui Liu, Zhifeng Wei, Yue Dai
Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine is easy to accumulate in gut, the largest endocrine organ in the body, attracts us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg/kg, i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and IL-17 level in blood...
June 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28634394/the-roles-of-toll-like-receptor-4-in-the-pathogenesis-of-pathogen-associated-biliary-fibrosis-caused-by-clonorchis-sinensis
#3
Chao Yan, Bo Li, Fang Fan, Ying Du, Rui Ma, Xiao-Dan Cheng, Xiang-Yang Li, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633868/daidzein-stimulates-osteogenesis-facilitating-proliferation-differentiation-and-antiapoptosis-in-human-osteoblast-like-mg-63-cells-via-estrogen-receptor-dependent-mek-erk-and-pi3k-akt-activation
#4
Xin Jin, Jing Sun, Bo Yu, Yue Wang, Wei Jia Sun, Jing Yang, Su Hui Huang, Wen Li Xie
Daidzein, a natural soy isoflavone, has a structure similar to estradiol and exhibiting bone-sparing effects against osteoporosis. However, the molecular mechanisms of osteogenesis remain unclear. We hypothesized that daidzein stimulates osteogenesis through estrogen receptor (ER)-dependent signal pathways. To test this hypothesis, we investigated the effects of daidzein compared with 17β-estradiol on proliferation, differentiation, and cisplatin-induced apoptosis in human osteoblast-like MG-63 cells containing 2 ER isoforms...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#5
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28631920/microfluidic-mapping-of-cancer-cell-protein-binding-interaction
#6
Zongbin Liu, Xin Han, Rui Chen, Kai Zhang, Ying Li, Shelby Fruge, Joon Hee Jang, Yuan Ma, Lidong Qin
The interaction between tumor cells and microenvironment during metastasis is mediated by the binding of cell surface receptors, such as integrins and selectins, with protein ligands. Delineation of their binding interaction and identification of key receptors may be particularly important both in understanding ECM remodeling and in developing potential therapeutic targets. Here we present a microfluidic chip that allows qualitative and quantitative mapping of large population cell-protein interaction. It was found that β1 integrin showed stronger binding interaction with collagen than with other ECM proteins...
June 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28629129/dietary-management-of-skin-health-the-role-of-genistein
#7
REVIEW
Natasha Irrera, Gabriele Pizzino, Rosario D'Anna, Mario Vaccaro, Vincenzo Arcoraci, Francesco Squadrito, Domenica Altavilla, Alessandra Bitto
In women, aging and declining estrogen levels are associated with several cutaneous changes, many of which can be reversed or improved by estrogen supplementation. Two estrogen receptors-α and β-have been cloned and found in various tissue types. Epidermal thinning, declining dermal collagen content, diminished skin moisture, decreased laxity, and impaired wound healing have been reported in postmenopausal women. Experimental and clinical studies in postmenopausal conditions indicate that estrogen deprivation is associated with dryness, atrophy, fine wrinkling, and poor wound healing...
June 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28626166/efficacy-of-denosumab-for-osteoporosis-in-three-female-patients-with-osteogenesis-imperfecta
#8
Masashi Uehara, Yukio Nakamura, Jun Takahashi, Mikio Kamimura, Shota Ikegami, Takako Suzuki, Shigeharu Uchiyama, Tomomi Yamaguchi, Tomoki Kosho, Hiroyuki Kato
Osteogenesis imperfecta (OI) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of OI to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#9
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28623179/modulation-of-tgf-%C3%AE-smad-and-erk-signaling-pathways-mediates-the-anti-fibrotic-effect-of-mirtazapine-in-mice
#10
Dalia M El-Tanbouly, Walaa Wadie, Rabab H Sayed
Serotonin (5-HT) has been implicated as a key driver of liver fibrosis, acting via 5-HT2 receptor activation in the hepatic stellate cells. The current study was conducted to investigate the effects of mirtazapine, a 5-HT2A antagonist, in a mouse model of liver fibrosis. Mice received thioacetamide (TAA, 150mg/kg/biweekly, ip) for nine successive weeks for induction of liver fibrosis. Administration of mirtazapine significantly improved the plasma aminotransferases, reduced hepatic 5-HT concentration and ameliorated TAA-induced liver fibrosis, as demonstrated by reduced portal blood pressure, liver procollagen I content and α alpha smooth muscle actin expression...
June 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28623125/chronic-intermittent-hypoxia-induces-liver-fibrosis-in-mice-with-diet-induced-obesity-via-tlr4-myd88-mapk-nf-kb-signaling-pathways
#11
Hyeon Hui Kang, In Kyoung Kim, Hye In Lee, Hyonsoo Joo, Jeong Uk Lim, Jongmin Lee, Sang Haak Lee, Hwa Sik Moon
Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622179/paucicellular-fibrointimal-proliferation-characterizes-pediatric-pulmonary-vein-stenosis-clinicopathologic-analysis-of-213-samples-from-97-patients
#12
Alexandra E Kovach, Philip M Magcalas, Christina Ireland, Kerry McEnany, Andre M Oliveira, Mark W Kieran, Christopher W Baird, Kathy Jenkins, Sara O Vargas
Pulmonary vein stenosis (PVS) is a luminal narrowing of extrapulmonary pulmonary veins. In pediatric patients, it arises following repair of congenital heart disease, particularly anomalous pulmonary venous return; in lung disease, especially prematurity; and rarely in isolation. The etiology is unknown and the course often fatal without lung transplantation. We hypothesized that systematic clinicopathologic review of pediatric PVS could provide further pathogenic insight. We included patients who underwent first resection of pulmonary venous tissue for symptomatic PVS at our pediatric referral center from 1995 to 2014...
June 15, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28621056/denervation-effectively-aggravates-rat-experimental-periodontitis
#13
X Yu, Z Gong, Q Lin, W Wang, S Liu, S Li
BACKGROUND: Nerve and its related factors in the occurrence and development of periodontitis are worthy of further study. Denervation research is a useful addition to nerve and innervation studies. The aim of this study is to establish a rat model of inferior alveolar nerve transection combined with ligature-induced periodontitis to elucidate the effects of denervation on ligature-induced rat periodontitis. MATERIAL AND METHODS: Sixty-four Wistar rats were distributed to the four groups randomly: ligation (L); denervation (D); ligation+denervation (LD); and normal (N) as control...
June 16, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#14
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
June 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28618934/identification-of-curcumin-inhibited-extracellular-matrix-receptors-in-non-small-cell-lung-cancer-a549-cells-by-rna-sequencing
#15
Huiping Li, Hongjin Wu, Hongfang Zhang, Ying Li, Shuang Li, Qiang Hou, Shixiu Wu, Shuan-Ying Yang
Curcumin is a potent anti-cancer drug in several types of human cancers. Despite of several preclinical and clinical studies of curcumin, the precise mechanism of curcumin in cancer prevention has remained unclear. In our study, we for the first time investigated whole transcriptome alteration in A549 non-small cell lung cancer (NSCLC) cell lines after treatment with curcumin using RNA sequencing. We found that lots of genes and signaling pathways were significantly altered after curcumin treatment in A549 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28616246/fibroblast-reticular-cells-engineer-a-blastema-extracellular-network-during-digit-tip-regeneration-in-mice
#16
Luis Marrero, Jennifer Simkin, Mimi Sammarco, Ken Muneoka
The regeneration blastema which forms following amputation of the mouse digit tip is composed of undifferentiated cells bound together by an organized network of fibers. A monoclonal antibody (ER-TR7) that identifies extracellular matrix (ECM) fibers produced by fibroblast reticular cells during lymphoid organogenesis was used to characterize the ECM of the digit, the blastema, and the regenerate. Digit fibroblast reticular cells produce an ER-TR7(+) ECM network associated with different tissues and represent a subset of loose connective tissue fibroblasts...
April 2017: Regeneration
https://www.readbyqxmd.com/read/28615031/leucine-rich-alpha-2-glycoprotein-promotes-th17-differentiation-and-collagen-induced-arthritis-in-mice-through-enhancement-of-tgf-%C3%AE-smad2-signaling-in-na%C3%A3-ve-helper-t-cells
#17
Hayato Urushima, Minoru Fujimoto, Takashi Mishima, Tomoharu Ohkawara, Hiromi Honda, Hyun Lee, Hirohisa Kawahata, Satoshi Serada, Tetsuji Naka
BACKGROUND: Leucine-rich alpha 2 glycoprotein (LRG) has been identified as a serum protein elevated in patients with active rheumatoid arthritis (RA). Although the function of LRG is ill-defined, LRG binds with transforming growth factor (TGF)-β and enhances Smad2 phosphorylation. Considering that the imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg) plays important roles in the pathogenesis of RA, LRG may affect arthritic pathology by enhancing the TGF-β-Smad2 pathway that is pivotal for both Treg and Th17 differentiation...
June 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28614795/a-3d-microfluidic-model-for-preclinical-evaluation-of-tcr-engineered-t-cells-against-solid-tumors
#18
Andrea Pavesi, Anthony T Tan, Sarene Koh, Adeline Chia, Marta Colombo, Emanuele Antonecchia, Carlo Miccolis, Erica Ceccarello, Giulia Adriani, Manuela T Raimondi, Roger D Kamm, Antonio Bertoletti
The tumor microenvironment imposes physical and functional constraints on the antitumor efficacy of adoptive T cell immunotherapy. Preclinical testing of different T cell preparations can help in the selection of efficient immune therapies, but in vivo models are expensive and cumbersome to develop, while classical in vitro 2D models cannot recapitulate the spatiotemporal dynamics experienced by T cells targeting cancer. Here, we describe an easily customizable 3D model, in which the tumor microenvironment conditions are modulated and the functionality of different T cell preparations is tested...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28611098/ticagrelor-and-eptifibatide-bolus-versus-ticagrelor-and-eptifibatide-bolus-with-2-hour-infusion-in-high-risk-acute-coronary-syndromes-patients-undergoing-early-percutaneous-coronary-intervention
#19
Moazez J Marian, Oluseun Alli, Firas Al Solaiman, Brigitta C Brott, Mark Sasse, Tara Leesar, Sumanth D Prabhu, Massoud A Leesar
BACKGROUND: In patients with non-ST-segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2-hour infusion is unknown. METHODS AND RESULTS: A total of 70 P2Y12-naïve patients, with high-risk non-ST-segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2-hour infusion (group 2)...
June 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28609704/sphingosine-1-phosphate-s1p-suppresses-the-collagen-induced-activation-of-human-platelets-via-s1p4-receptor
#20
Takashi Onuma, Kumiko Tanabe, Yuko Kito, Masanori Tsujimoto, Kodai Uematsu, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Tomoaki Doi, Kiyoshi Nagase, Shigeru Akamatsu, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation...
June 2, 2017: Thrombosis Research
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