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Xuesong Zhao, Xin Ren, Baixiang Ren, Zhouying Luo, Rong Zhu
2,2,4',4'-Tetrabromodi-phenyl ether (BDE-47) is predominantly concentrated in humans and wildlife and disturbs thyroid hormone homeostasis. The purpose of this study was to characterize the thyroid endocrine disruption induced by life-cycle exposure to BDE-47 in adults and offspring of zebrafish (Danio rerio). We exposed zebrafish embryos at the blastula stage to different concentrations of BDE-47 (1, 5, and 10μg/L). Exposure duration was 180days until fish reached adulthood. In F0 larvae, exposure decreased survival and increased malformations at 4 dpf...
October 12, 2016: Environmental Toxicology and Pharmacology
Zoe Daniel, Angelina Swali, Richard Emes, Simon C Langley-Evans
BACKGROUND: Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. METHODS: Pregnant rats were fed control or a low protein diet from conception to day 13 gestation...
2016: Genes & Nutrition
Danielle L Brunjes, Adam Castano, Autumn Clemons, Jonah Rubin, Mathew S Maurer
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques...
October 18, 2016: Journal of Cardiac Failure
Xing-Hui Gao, Lu Tian, Jiong Wu, Xiao-Lu Ma, Chun-Yan Zhang, Yan Zhou, Yun-Fan Sun, Bo Hu, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) patients undergoing curative resection. METHODS: MDSCs were measured by flow cytometry. The correlation between MDSCs and tumor recurrence were analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015...
October 20, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Akihiko Hosoi, Yu Su, Masaharu Torikai, Hirofumi Jono, Daisuke Ishikawa, Kenji Soejima, Hirofumi Higuchi, Jianying Guo, Mitsuharu Ueda, Genki Suenaga, Hiroaki Motokawa, Tokunori Ikeda, Satoru Senju, Toshihiro Nakashima, Yukio Ando
Familial amyloidotic polyneuropathy (FAP) is a systemic amyloidosis mainly caused by amyloidogenic transthyretin (ATTR). This incurable disease causes death approximately 10 years after onset. Although it has been widely accepted that conformational change of the monomeric form of transthyretin (TTR) is very important for amyloid formation and deposition in the organs, no effective therapy targeting this step is available. In this study, we generated a mouse monoclonal antibody T24 which recognized the cryptic epitope of conformationally-changed TTR...
October 7, 2016: Journal of Biological Chemistry
Xiao-Yan Cai, Xiao-Chun Ni, Yong Yi, Hong-Wei He, Jia-Xing Wang, Yi-Peng Fu, Jian Sun, Jian Zhou, Yun-Feng Cheng, Jian-Jun Jin, Jia Fan, Shuang-Jian Qiu
Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39Foxp3 regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection.Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection...
October 2016: Medicine (Baltimore)
Jun Shao, Yong Yao
PURPOSE: The apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear. METHODS: Natural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs)...
2016: Molecular Vision
Ho Il Yoon, Oh-Ran Kwon, Kyung Nam Kang, Yong Sung Shin, Ho Sang Shin, Eun Hee Yeon, Keon Young Kwon, Ilseon Hwang, Yoon Kyung Jeon, Yongdai Kim, Chul Woo Kim
BACKGROUND: Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. METHODS: We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets...
September 2016: Journal of Cancer Prevention
John J Chen, Joseph C Genereux, Eul Hyun Suh, Vincent F Vartabedian, Bibiana Rius, Song Qu, Maria T A Dendle, Jeffery W Kelly, R Luke Wiseman
Transthyretin (TTR) is a tetrameric serum protein associated with multiple systemic amyloid diseases. In these disorders, TTR aggregates in extracellular environments through a mechanism involving rate-limiting dissociation of the tetramer to monomers, which then misfold and aggregate into soluble oligomers and amyloid fibrils that induce toxicity in distal tissues. Using an assay established herein, we show that highly destabilized, aggregation-prone TTR variants are secreted as both native tetramers and non-native conformations that accumulate as high-molecular-weight oligomers...
October 20, 2016: Cell Chemical Biology
Kylie Mueller, Nijole Bernaitis, Tony Badrick, Shailendra Anoopkumar-Dukie
The HAS-BLED model is widely utilised to assess patients' bleed risk prior to anticoagulant therapy including warfarin. Some of the variables assessed in the model are also known to influence warfarin control, commonly measured by time in therapeutic range (TTR). The aim of the study was to determine if the HAS-BLED risk tool is a good predictor of bleed risk and warfarin control in deep vein thrombosis (DVT) patients. Retrospective data were collected for DVT warfarin care patients at Sullivan Nicolaides Pathology...
October 8, 2016: Basic & Clinical Pharmacology & Toxicology
Ayrton Massaro, Robert P Giugliano, Bo Norrving, Ali Oto, Roland Veltkamp
Atrial fibrillation is the world's most common sustained cardiac arrhythmia and is associated with a significantly increased risk of stroke. The global burden of atrial fibrillation is rising, commensurate with the ageing population. Well-controlled vitamin K antagonist-based anticoagulation has been shown to reduce the risk of stroke secondary to atrial fibrillation by two-thirds. However, patients with atrial fibrillation have frequently been denied anticoagulation because of a variety of perceived risks related to bleeding, falls, chronological age, and poor compliance...
October 4, 2016: International Journal of Stroke: Official Journal of the International Stroke Society
Genki Suenaga, Tokunori Ikeda, Yoshihiro Komohara, Koutaro Takamatsu, Tatsuyuki Kakuma, Masayoshi Tasaki, Yohei Misumi, Mitsuharu Ueda, Takaaki Ito, Satoru Senju, Yukio Ando
We hypothesized that tissue-resident macrophages in familial amyloid polyneuropathy (FAP) patients will exhibit qualitative or quantitative abnormalities, that may accelerate transthyretin (TTR)-derived amyloid deposition. To evaluate this, we examined the number and subset of tissue-resident macrophages in heart tissue from amyloid-deposited FAP and control patients. In both FAP and control patients, tissue-resident macrophages in heart tissue were all Iba+/CD163+/CD206+ macrophages. However, the number of macrophages was significantly decreased in FAP patients compared with control patients...
2016: PloS One
Sarah M Alyousif, Ahmed A Alsaileek
BACKGROUND: Atrial fibrillation (AF) is the most common chronic rhythm disorder. Patients with AF are at an increased risk of ischemic stroke. Therefore, optimal anticoagulation is essential to reduce the risk of stroke. The aim of this study was to assess the level of anticoagulation control achieved in patients with nonvalvular AF receiving medical care in a tertiary care hospital. METHODS: This was a retrospective cohort study in ambulatory care clinics at tertiary care hospital in Saudi Arabia...
October 2016: Journal of the Saudi Heart Association
Lori J Wirth, Shaker Dakhil, Gabriela Kornek, Rita Axelrod, Douglas Adkins, Shubham Pant, Paul O'Brien, Philip R Debruyne, Kelly S Oliner, Jun Dong, Swami Murugappan
OBJECTIVE: This phase 2 estimation study evaluated docetaxel/cisplatin with/without panitumumab, an anti-epidermal growth factor receptor monoclonal antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Randomized patients received docetaxel/cisplatin (75mg/m(2) each) with/without panitumumab (9mg/kg) in 21-day cycles. Patients randomized to panitumumab+chemotherapy could continue panitumumab monotherapy after completing six chemotherapy cycles without progression; patients randomized to chemotherapy alone could receive second-line panitumumab after progression...
October 2016: Oral Oncology
Jiri Volf, Ondrej Polansky, Karolina Varmuzova, Lenka Gerzova, Zuzana Sekelova, Marcela Faldynova, Vladimir Babak, Matej Medvecky, Adrian L Smith, Bernd Kaspers, Philippe Velge, Ivan Rychlik
In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12-2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens...
2016: PloS One
José Miguel Rivera-Caravaca, Inmaculada Viedma-Viedma, Vanessa Roldán
INTRODUCTION: Treatment of venous thromboembolism (VTE) is classically based on oral vitamin K antagonists (VKAs). Due to the disadvantages and side effects of these drugs, monitoring the quality of anticoagulation by assessing time within therapeutic range (TTR) is recommended. Variables altering the TTR in patients with VTE are yet to be determined. The aim of this study was to analyze the quality of anticoagulation in patients with VTE treated with VKAs and to identify factors associated with poor-quality anticoagulation...
September 28, 2016: Biological Research for Nursing
Laura C Halder, Laura B Richardson, Ross F Garberich, Peter Zimbwa, Mosi K Bennett
Left ventricular assist devices (LVADs) require anticoagulation therapy with vitamin K antagonists to reduce the risk of thrombotic events. The quality of anticoagulation may be assessed by the time in therapeutic range (TTR). We analyzed a retrospective cohort of LVAD patients at a single institution from January 2012 to September 2014. Primary outcomes included TTR during the study time period and TTR 30 days preceding a bleeding or thrombotic event. Fifty-one patients (mean age 57.0 ± 14.6 years; 78% male) had an overall TTR of 52%...
September 22, 2016: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Nijole Bernaitis, Chi Keong Ching, Liping Chen, Jin Shing Hon, Siew Chong Teo, Andrew K Davey, Shailendra Anoopkumar-Dukie
BACKGROUND: Warfarin reduces stroke risk in atrial fibrillation (AF) patients but requires ongoing monitoring. Time in therapeutic range (TTR) is used as a measure of warfarin control, with a TTR less than 60% associated with adverse patient outcomes. The Sex, Age, Medical history, Treatment, Tobacco use, Race (SAMe-TT2R2) score has been identified as a model able to predict warfarin control, but this has been tested in mainly Caucasian populations. Therefore, the aim of this study was to determine the ability of the SAMe-TT2R2 score to predict warfarin control in a Singaporean population consisting of Chinese, Malay, and Indian race...
September 23, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Ana Rocha, Luísa Lobato
Orthotopic liver transplantation (LT) was implemented as the inaugural disease-modifying therapy for hereditary transthyretin (ATTR) amyloidosis, a systemic amyloidosis mainly affecting the peripheral nervous system and heart. The first approach to pharmacologic therapy was focused on the stabilization of the TTR tetramer; following that new advent LT was assumed as the second step of treatment, for those patients whose neuropathy becomes worse after a course of pharmacologic therapy. The renal disease has been ignored in hereditary ATTR amyloidosis...
September 14, 2016: Transplantation Reviews
Jin Zhang, Afshan Begum, Kristoffer Brännström, Christin Grundström, Irina Iakovleva, Anders Olofsson, A Elisabeth Sauer-Eriksson, Patrik L Andersson
Thyroid disruption by xenobiotics is associated with a broad spectrum of severe adverse outcomes. One possible molecular target of thyroid hormone disrupting chemicals (THDCs) is transthyretin (TTR), a thyroid hormone transporter in vertebrates. To better understand the interactions between TTR and THDCs, we determined the crystallographic structures of human TTR in complex with perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2,2',4,4'-tetrahydroxybenzophenone (BP2). The molecular interactions between the ligands and TTR were further characterized using molecular dynamics simulations...
October 10, 2016: Environmental Science & Technology
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