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HR pathway

Yongyue Wei, Paula Tejera, Zhaoxi Wang, Ruyang Zhang, Feng Chen, Li Su, Xihong Lin, Ednan K Bajwa, B Taylor Thompson, David C Christiani
RATIONALE: Platelets are believed to contribute to the acute respiratory distress syndrome (ARDS) pathogenesis through inflammatory coagulation pathways. We recently reported that LRRC16A modulates baseline platelet counts to mediate ARDS risk. OBJECTIVES: To examine the role of LRRC16A in ARDS survival and its mediating effect through platelets. METHODS: 414 ARDS cases from intensive care unit (ICU) were recruited which had exome-wide genotyping data, detailed platelet counts and follow-up data during ICU hospitalizaiton...
October 21, 2016: American Journal of Respiratory and Critical Care Medicine
Elizabeth M Dlugosz, Scott C Lenaghan, C Neal Stewart
Over the last decade there has been a resurgence in the use of plant protoplasts that range from model species to crop species, for analysis of signal transduction pathways, transcriptional regulatory networks, gene expression, genome-editing, and gene-silencing. Furthermore, significant progress has been made in the regeneration of plants from protoplasts, which has generated even more interest in the use of these systems for plant genomics. In this work, a protocol has been developed for automation of protoplast isolation and transformation from a 'Bright Yellow' 2 (BY-2) tobacco suspension culture using a robotic platform...
September 27, 2016: Journal of Visualized Experiments: JoVE
Tahar Ait-Ali, Ivan Díaz, Ferran Soldevila, Esmeralda Cano, Yanli Li, Alison D Wilson, Bruno Giotti, Alan L Archibald, Enric Mateu, Laila Darwich
Little is known about the host factor in the response to PRRSV vaccination. For this purpose, piglets were immunized with a commercial PRRSV-live vaccine and classified as high responders (HR) or low responders (LR) as regards to the frequencies of virus-specific IFN-γ-secreting cells. Six weeks post vaccination, PBMCs isolated from three individuals with the most extreme responses in each HR and LR groups and 3 unvaccinated controls, were either stimulated with phytohaemagglutinin, challenged with the vaccine or mock treated for 24 h, prior conducting transcriptional studies, gene ontology and pathway analyses...
October 20, 2016: Veterinary Research
Hamid Reza Rahimi, Amir Hooshang Mohammadpour, Mostafa Dastani, Mahmoud Reza Jaafari, Khalil Abnous, Majid Ghayour Mobarhan, Reza Kazemi Oskuee
OBJECTIVE: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both or insulin resistance. Curcumin inhibits NF-κB signaling pathway. The aim of this study is evaluation of the effect of Nano-curcumin on HbA1C, fast blood glucose and lipid profile in diabetic patients. MATERIALS AND METHODS: Seventy type-2 diabetic patients (fasting blood glucose (FBG) ≥ 126 mg/dL or 2-hr postprandial blood glucose ≥200 mg/dl) randomly receivedeither Curcumin (as nano-micelle 80 mg/day) or placebo for 3 months in a double blind randomized clinical trial...
September 2016: Avicenna Journal of Phytomedicine
Mi-Sun Kwon, Jaewon Min, Hee-Yeon Jeon, Kwangwoo Hwang, Chuna Kim, Junho Lee, Je-Gun Joung, Woong-Yang Park, Hyunsook Lee
BRCA2 is a multifunctional tumor suppressor involved in homologous recombination (HR), mitotic checkpoint regulation, and telomere homeostasis. Absence of Brca2 in mice results in progressive shortening of telomeres and senescence, yet cells are prone to neoplastic transformation with elongated telomeres, suggesting that BRCA2 has positive and negative effects on telomere length regulation along the path to tumorigenesis. Using Caenorhabditis elegans as a model, we show here that depletion of BRC-2, an ortholog of BRCA2, paradoxically delays senescence in telomerase-deficient mutant worms...
October 2016: FEBS Open Bio
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Takahisa Suzuki, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Seiichiro Ozono, Hideo Yasuda
Circulating renin-angiotensin system (RAS) activation is maintained after renal function has deteriorated. The activation of the intrarenal RAS plays a critical role in the pathophysiology of chronic kidney disease (CKD), independently of the circulating RAS. However, the activation of intrarenal RAS and the chymase-dependent pathway after initiation of dialysis has not been clarified. We recruited 19 CKD patients (10 without dialysis and 9 with dialysis) who underwent a heminephrectomy. Circulating RAS was investigated before nephrectomy...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Jessica E Middlemiss, Carmel M McEniery
Obesity is an ongoing global epidemic and has adverse consequences for cardiovascular health. Obesity is often associated with hypertension, which is, itself, a common condition and an important cause of morbidity and mortality worldwide. Although animal models of obesity have provided extensive data on the links between obesity and hypertension, a greater understanding of the pathways linking obesity and hypertension in humans is likely to assist translation of animal data, and may, itself, identify important treatment strategies...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Shigeru Shibata, Kenichi Ishizawa, Shunya Uchida
The kidney has a central role in long-term control of blood pressure, and decreased kidney function is a common but difficult-to-treat cause of hypertension. Conversely, elevated blood pressure contributes to the progression of chronic kidney disease. Steroid hormone aldosterone and its receptor mineralocorticoid receptor (MR) contribute to hypertension by increasing renal salt reabsorption and promote kidney dysfunction through direct effects on renal parenchymal cells. Accumulating data indicate that various mechanisms affect aldosterone-MR signaling...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Julia Smedbråten, Geir Mjøen, Anders Hartmann, Anders Åsberg, Halvor Rollag, Tom Eirik Mollnes, Leiv Sandvik, Morten W Fagerland, Steffen Thiel, Solbjørg Sagedal
BACKGROUND: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient's native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation. METHODS: Two mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000-2001...
October 18, 2016: BMC Nephrology
Lu Chen, Courtney A Kurtyka, Eric A Welsh, Jason I Rivera, Brienne E Engel, Teresita Muñoz-Antonia, Sean J Yoder, Steven A Eschrich, Ben C Creelan, Alberto A Chiappori, Jhanelle E Gray, Jose Luis Ramirez, Rafael Rosell, Matthew B Schabath, Eric B Haura, Dung-Tsa Chen, W Douglas Cress
Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues...
October 14, 2016: Oncotarget
A Drouillard, F Puleo, J B Bachet, S Ouazzani, A Calomme, P Demetter, G Verset, J L Van Laethem, R Maréchal
BACKGROUND: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins...
October 18, 2016: British Journal of Cancer
Joon Kyungjoon Lim, Sandra Burke, Geoffrey Head
OBJECTIVE: Obesity during pregnancy is associated with a greater risk of developing hypertension in the offspring. Plasma leptin levels correlate strongly with blood pressure and renal sympathetic nerve activity (RSNA). The ventromedial hypothalamus (VMH) is a key centre of energy homeostasis, haemodynamic and sympathetic tone to renal vasculature. It is possible that exposure to over-nutrition during development change the activity of the neurons, amplifying sympathetic output leading to hypertension in the offspring...
September 2016: Journal of Hypertension
Sekib Sokolovic, Samir Mehmedagic
OBJECTIVE: The goal of this paper was to present the effects of the vagus nerve stimulation (VNS) on a blood pressure (BP) and heart rate (HR) in arterial hypertension patient. DESIGN AND METHOD: The pilot study (SPM-005) was designed to evaluate the eficiancy and safety profile of the neurostimulation of the cholinergic anti-inflammatory pathways using the active implantable device for the vagus nerve stimulation in rheumatoid arthritis patient. We investigated the VNS on the BP and HR in 68 years old female patient with a long-standing arterial hypertension and the lisinopril and hydrochlorothiazide in a therapy...
September 2016: Journal of Hypertension
Richard Wainford, Casey Carmichael, Kathryn Walsh
OBJECTIVE: We have demonstrated a critical role of CNS Gαi2 proteins in sodium homeostasis and blood pressure regulation. These studies tested the hypothesis that increased total body sodium activates the afferent renal afferent nerves to evoke sympathoinhibition to facilitate sodium homeostasis and normotension, via a PVN signal transduction pathway involving Gαi2 proteins, in the Sprague-Dawley (SD) rat. DESIGN AND METHOD: Conscious SD rats, having undergone sham or renal afferent nerve denervation (Renal-CAP) underwent an IV volume expansion (VE; 5% BW), HR, MAP, natriuresis and PVN neuronal activation were assessed (N = 5/group)...
September 2016: Journal of Hypertension
Ching-Hsiao Lee, Yuh-Shuen Chen, Chien-Wei Hou, Kee-Ching Jeng, Kuo-Shu Chen
OBJECTIVES: Longan seeds have been used as a folk medicine in China. Longan seed extract (LSE) is known for antioxidative, antiproliferative, hypoglycemic, and hypouremic effects. However, its anti-inflammatory effect has not been shown. MATERIALS AND METHODS: In this study, Sprague-Dawley (SD) rats were given LSE orally (vehicle, 10, and 30 mg/kg) for 3 days to its test anti-inflammatory effect by injecting λ-carrageenan (CARR) in the right hind paw or lipopolysaccharide (LPS), IP...
August 2016: Iranian Journal of Basic Medical Sciences
Jung-Jyh Hung, Shiu-Feng Huang, Ying-Ying Shen, Yu-Chung Wu, Teh-Ying Chou, Wen-Hu Hsu
BACKGROUND: The programmed cell death-ligand 1 (PD-L1) pathway plays an important role in maintaining immune homeostasis. The PD-L1 pathway may also protect tumors from attack by cytotoxic T cells. Blockade of programmed cell death 1 (PD1) or PD-L1 induced durable tumor regression in patients with advanced cancers, including non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 expression in patients with lung adenocarcinoma remains controversial. METHODS: A total of 112 patients with resected lung adenocarcinoma were included in the study...
October 12, 2016: Annals of Thoracic Surgery
Jiawei Guan, Qian Zhao, Weifeng Mao
PTEN is a tumor suppressor gene characterized as a phosphatase that antagonizes the phosphatidylinositol 3-kinase signaling pathway in the cytoplasm. Nuclear PTEN plays roles in chromosomal stability, in which the double-strand breaks (DSB) repair mediated by homologous recombination (HR) and non-homologous end joining (NHEJ) is critical. Herein, the role of nuclear PTEN in DSB repair and the underlying molecular mechanism was investigated in this study. Using human breast cancer BT549 and MDA-MB-231 cell lines, we reveal a specific feature of PTEN that controls poly(ADP-ribosyl)ation of Ku70 and interferes with binding of Ku70 at DSB...
October 11, 2016: Biochimica et Biophysica Acta
Olga Villamar Cruz, Tatiana Y Prudnikova, Daniela Araiza-Olivera, Carlos Perez-Plasencia, Neil Johnson, Andrea J Bernhardy, Michael Slifker, Catherine Renner, Jonathan Chernoff, Luis E Arias-Romero
Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors...
October 11, 2016: Oncotarget
Wynand Paul Roos, Andrea Krumm
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair...
October 13, 2016: Nucleic Acids Research
Jilong Wang, Suthamat Niyompanich, Yi-Shu Tai, Jingyu Wang, Wenqin Bai, Prithviraj Mahida, Tuo Gao, Kechun Zhang
: Chromosomal integration of heterologous metabolic pathways is optimal for industrially relevant fermentation, as plasmid-based fermentation causes extra metabolic burden and genetic instabilities. In this work, chromosomal integration was adapted for the production of mevalonate which can be readily converted into β-methyl-δ-valerolactone, a monomer for the production of mechanically tunable polyesters. The mevalonate pathway driven by a constitutive promoter was integrated into the chromosome of Escherichia coli to replace the native fermentation gene adhE or ldhA The engineered strains (CMEV-1 and CMEV-2) did not require inducer or antibiotic, and showed slightly higher maximal productivities (0...
October 7, 2016: Applied and Environmental Microbiology
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