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Clinical Science (1979-)

A Augusto Peluso, Jesper Bork Bertelsen, Kenneth Andersen, Tenna Pavia Mortensen, Pernille B Hansen, Colin Sumners, Michael Bader, Robson A Santos, U Muscha Steckelings
The angiotensin AT2 receptor (AT2 R) promotes vasodilation by nitric oxide (NO) release from endothelial cells. However, the mechanisms underlying the AT2 R-induced stimulation of endothelial NO synthase (eNOS) is still not completely understood. Therefore, we investigated whether in addition to the known AT2 R-mediated phosphorylation of eNOS at Ser1177, activation of phosphatases and dephosphorylation of eNOS at Tyr657 and Thr495 are also involved. Human Aortic Endothelial Cells (HAEC) were stimulated with the AT2 R-agonist C21 (1µM) in the presence or absence of either PD123319 (10µM; AT2 R-antagonist), L-NAME (10µM; eNOS inhibitor), MK-2206 (100nM; Akt-inhibitor) sodium fluoride (1nM; serine/threonine-phosphatase inhibitor) or sodium orthovanadate (10nM; tyrosine-phosphatase inhibitor)...
March 14, 2018: Clinical Science (1979-)
Zhen-Guo Ma, Xin Zhang, Yu-Pei Yuan, Ya-Ge Jin, Ning Li, Chun-Yan Kong, Peng Song, Qi-Zhu Tang
T cell infiltration and the subsequently increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure. A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cells-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro...
March 14, 2018: Clinical Science (1979-)
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
Zihao Chen, Hongping Ju, Shan Yu, Ting Zhao, Xiaojie Jing, Ping Li, Jing Jia, Nan Li, Bibo Tan, Yong Li
Gastric cancer (GC) is one of a major global health problem especially in Asia. Nowadays, long non-coding RNA has gained significantly attention in the current research climate such as carcinogenesis. This research desired to explore the mechanism of Prader-Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level was detected by qRT-PCR and western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by CCK8, flow cytometry, wound healing and transwell assay...
March 13, 2018: Clinical Science (1979-)
Xiao Wang, Huarong Wang, Wei Liu, Zhiyuan Zhang, Yanhao Zhang, Wenqiang Zhang, Zijiang Chen, Guoliang Xia, Chao Wang
Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9%-18% of reproductive-age women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation...
March 13, 2018: Clinical Science (1979-)
Chang Liu, Congcong Zhang, Lixin Jia, Boya Chen, Luxin Liu, Jie Sun, Wenmei Zhang, Bin You, Yulin Li, Ping Li, Jie Du
Thoracic aortic aneurysm and dissection (TAAD) is due to degeneration of the aorta and causes a high mortality rate, while molecular mechanisms for the development of TAAD are still not completely understood. In this study, 3-aminopropionitrile (BAPN) treatment was used to induce TAAD mouse model. Through transcriptome analysis, we found the expression levels of genes associated with interleukin-3 (IL-3) signaling pathway were upregulated during TAAD development in mouse, which were validated by real-time PCR...
March 9, 2018: Clinical Science (1979-)
Seungbum Kim, Ruby Goel, Ashok Kumar, Yanfei Qi, Gil Lobaton, Koji Hosaka, Mohammed Mohammed, Eileen M Handberg, Elaine M Richards, Carl J Pepine, Mohan K Raizada
Recent evidence indicates a link between gut pathology and microbiome with hypertension in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in this study were to test the hypotheses that high blood pressure patients have distinct gut microbiomes and that gut epithelial barrier function markers and microbiome composition could predict systolic blood pressure. Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high blood pressure and reference subjects...
March 5, 2018: Clinical Science (1979-)
Magaiver Andrade-Silva, Marcos Antônio Cenedeze, Luiz Augusto Perandini, Raphael José Ferreira Felizardo, Ingrid Mizuno Watanabe, Juan Sebastian Henao Agudelo, Ângela Castoldi, Giselle Martins Gonçalves, Clarice Silvia Taemi Origassa, Patricia Semedo, Meire Ioshie Hiyane, Orestes Foresto Neto, Denise Maria Avancini Costa Malheiros, Marlene Antonia Reis, Clarice Kazue Fujihara, Roberto Zatz, Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara, Danilo Candido de Almeida
Acute kidney injury (AKI) is considered an inflammatory disease in which Toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, this study aimed evaluate the specific participation of TLR2 and TLR4 molecules on development of cisplatin-induced AKI...
March 2, 2018: Clinical Science (1979-)
Douglas M Bennion, Chad H Jones, Alex N Dang, Jacob D Isenberg, Justin T Graham, Lena Lindblad, Oliver Domenig, Michael F Waters, Marko Poglitsch, Colin Sumners, U Muscha Steckelings
Significant neuroprotective effects of angiotensin II type 2 (AT2 ) receptor agonists in ischemic stroke have been previously demonstrated in multiple studies.  However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular and systemic administration, are unsuitable for translation to humans; in the latter case because AT2 receptor agonists are blood brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the blood brain barrier and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1-induced ischemic stroke...
March 2, 2018: Clinical Science (1979-)
Al Muktafi Sadi, Talat Afroze, M Ahsan Siraj, Abdul Momen, Colin White-Dzuro, Dorrin Zarrin-Khat, Shivalika Handa, Kiwon Ban, M Golam Kabir, Maria G Trivieri, Robert Gros, Peter Backx, Mansoor Husain
Background:  Heart failure (HF) is associated with reduced expression of plasma membrane Ca2+ -ATPase 4 (PMCA4).  Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin.  Here we examine temporally-regulated cardiac-specific over-expression of hPMCA4b in mouse models of myocardial ischemia reperfusion injury (IRI) ex vivo , and HF following experimental myocardial infarction (MI) in vivo Methods & Results: Doxycycline-regulated cardiomyocyte-specific overexpression and activity of hPMCA4b produced adaptive changes in expression levels of Ca2+ -regulatory genes, and induced hypertrophy without significant differences in Ca2+ transients or diastolic Ca2+ concentrations...
February 27, 2018: Clinical Science (1979-)
Stephanie Skuby Chassen, Veronique Ferchaud-Roucher, Madhulika B Gupta, Thomas Jansson, Theresa L Powell
Fatty acids (FA) are critical for fetal brain development and are transferred across the placenta by membrane-bound FA transport proteins (FATP), translocases (FAT/CD36) and cytosolic binding proteins (FABP). The cytosolic protein perilipin-2 aids in neutral lipid storage within lipid droplets. Decreased placental nutrient transport is believed to contribute to intrauterine growth restriction (IUGR); however, IUGR placental lipid transport and metabolism are poorly understood. We hypothesized protein expression of FATPs, FABPs, and perilipin-2 in human placenta is decreased and placental lipid content and incorporation into lipid classes are reduced in IUGR...
February 20, 2018: Clinical Science (1979-)
Shao-Jung Hsu, Ming-Hung Tsai, Ching-Chih Chang, Yu-Hsin Hsieh, Hui-Chun Huang, Fa-Yauh Lee, Chiao-Lin Chuang, Ming-Chih Hou, Shou-Dong Lee
Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. This study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process.Male Spraque-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, TAA cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction...
February 15, 2018: Clinical Science (1979-)
Bo Hang, Yunshan Wang, Yurong Huang, Pin Wang, Sasha A Langley, Lei Bi, Altaf H Sarker, Suzaynn F Schick, Christopher Havel, Peyton Jacob, Neal Benowitz, Hugo Destaillats, Xiaochen Tang, Yankai Xia, Kuang-Yu Jen, Lara A Gundel, Jian-Hua Mao, Antoine Snijders
Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to-7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and multiplicity, compared to controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation...
February 12, 2018: Clinical Science (1979-)
Dolores Olivares, Javier Perez-Hernandez, Maria J Forner, Cristina Pérez-Soriano, Maria C Tormos, Guillermo T Sáez, Felipe J Chaves, Josep Redón, Raquel Cortés
Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of this study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls...
February 12, 2018: Clinical Science (1979-)
Benjamin Leporq, Jean-Luc Daire, Catherine M Pastor, Pierre Deltenre, Christine Sempoux, Sabine Schmidt, Bernard E Van Beers
The purpose of this study was to develop and perform initial validation of dynamic MR imaging enhanced with gadoxetic acid as hepatobiliary contrast agent to quantify hepatic perfusion and hepatocyte function in patients with chronic liver disease. Free-breathing, dynamic gadoxetic acid-enhanced MR imaging was performed at 3.0 T using a three-dimensional time-resolved angiography sequence with stochastic trajectories during 38 minutes. A dual-input three-compartment model was developed to derive hepatic perfusion and hepatocyte function parameters...
February 12, 2018: Clinical Science (1979-)
Paul Emmanuel Vanderriele, Brasilina Caroccia, Teresa Maria Seccia, Maria Piazza, Livia Lenzini, Francesca Torresan, Maurizio Iacobone, Thomas Unger, Gian Paolo Rossi
The angiotensin II type 2 receptor (AT2R) and the angiotensin-(1-7) receptor (MasR) play a cardiovascular protective role by counter-regulating angiotensin II type 1 receptor (AT1R)-mediated effects, but whether this involves blunting of adrenocortical hormone secretion is unknown. We investigated the presence of AT1R, AT2R and MasR in aldosterone-producing adenoma (APA), a condition featuring hyperaldosteronism, and in APA-adjacent tissue. The effect of C21, an AT2R agonist, on CYP11B1 (cortisol synthase) and CYP11B2 (aldosterone synthase) gene expression in NCI-H295R and HAC15 cell lines, and in APA and APA-adjacent tissue was also assessed using the AT1R antagonist irbesartan to ascertain the specificity of C21 effect...
February 7, 2018: Clinical Science (1979-)
Anna K J Gradel, Max Salomonsson, Charlotte M Sørensen, Niels-Henrik Holstein-Rathlou, Lars J Jensen
Rationale: Abdominal obesity and/or a high intake of fructose may cause hypertension. K + channels, Na/K-ATPase, and voltage-gated Ca 2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K + transporters in long-term diet-induced hypertension in rats. Hypothesis: A 28-week diet rich in fat, fructose, or both, will lead to changes in K + transporter expression and function, which is associated with increased blood pressure and decreased arterial function...
February 7, 2018: Clinical Science (1979-)
Luciene Cristina Gastalho Campos, João Carlos Ribeiro-Silva, Alessandra Santos Menegon, Valerio Garrone Barauna, Ayumi Aurea Miyakawa, Jose Eduardo Krieger
Vein graft failure limits the long-term patency of the saphenous vein used as a conduit for coronary artery bypass graft. Early graft adaptation involves some degree of intima hyperplasia to sustain the hemodynamic stress, but the progress to occlusion in some veins remains unclear. We have demonstrated that stretch-induced up-regulation of cysteine and glycine-rich protein 3 (Crp3) in rat jugular vein and human saphenous vein in response to arterialization. Here, we developed a Crp3-KO rat to investigate the role of Crp3 in vascular remodeling...
February 2, 2018: Clinical Science (1979-)
Surya Ramachandran, Vinitha Anandan, V Raman Kutty, Ajit Mullasari, M Radhakrishna Pillai, C C Kartha
Growing evidence implicates cyclophilin A secreted by vascular wall cells and monocytes as a key mediator in atherosclerosis. Cyclophilin A in addition to its proliferative effects, during hyperglycaemic conditions, increases lipid uptake in macrophages by increasing scavenger receptors on the cell's surface. It also promotes macrophage migration across endothelial cells and conversion of macrophages to foam cells. Given the known effects of metformin in reducing vascular complications of diabetes, we investigated the effect of metformin on cyclophilin A action in macrophages...
January 30, 2018: Clinical Science (1979-)
Sabrina M Scroggins, Donna A Santillan, Jenna M Lund, Jeremy A Sandgren, Lindsay K Krotz, Wendy S Hamilton, Eric J Devor, Heather A Davis, Gary L Pierce, Katherine N Gibson-Corley, Curt D Sigmund, Justin L Grobe, Mark K Santillan
The pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in preeclampsia in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of preeclampsia in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human preeclampsia...
January 25, 2018: Clinical Science (1979-)
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