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M Garrido, C Escobar, C Zamora, C Rejas, J Varas, C Córdova, C Papuzinski, M Párraga, S San Martín, S Montedonico
Purpose: Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods: Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks...
2018: Stem Cells International
Elizabeth Harford-Wright, Julie Gavard
Glioblastoma multiforme are mortifying brain tumors that contain a subpopulation of tumor cells with stem-like properties, termed as glioblastoma stem-like cells (GSCs). These GSCs constitute an autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. A new therapeutic strategy would consist of targeting the GSC population. The GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells thereby involved in bidirectional molecular and cellular interactions...
2018: Journal of Experimental Neuroscience
Élie Besserer-Offroy, Patrick Bérubé, Jérôme Côté, Alexandre Murza, Jean-Michel Longpré, Robert Dumaine, Olivier Lesur, Mannix Auger-Messier, Richard Leduc, Éric Marsault, Philippe Sarret
The apelinergic system is an important player in the regulation of both vascular tone and cardiovascular function, making this physiological system an attractive target for drug development for hypertension, heart failure and ischemic heart disease. Indeed, apelin exerts a positive inotropic effect in humans whilst reducing peripheral vascular resistance. In this study, we investigated the signaling pathways through which apelin exerts its hypotensive action. We synthesized a series of apelin-13 analogs whereby the C-terminal Phe13 residue was replaced by natural or unnatural amino acids...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jia Zhang, Jiming Yin, Yangjia Wang, Bin Li, Xiangjun Zeng
The cause of the invalid reaction of smooth muscle cells to mechanical stimulation that results in a dysfunctional myogenic response that mediates the disruption of renal blood flow (RBF) in diabetic patients is debatable. The present study revealed that increased apelin concentration in serum of diabetic mice neutralized the myogenic response mediated by apelin receptor (APJ) and resulted in increased RBF, which promoted the progression of diabetic nephropathy. The results showed that apelin concentration, RBF, and albuminuria:creatinine ratio were all increased in kkAy mice, and increased RBF correlated positively to serum apelin both in C57 and diabetic mice...
March 9, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Elham Karimi, Ashraf Moini, Mehdi Yaseri, Nooshin Shirzad, Mahdi Sepidarkish, Mojgan Hossein-Boroujerdi, Mohammad Javad Hosseinzadeh-Attar
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women of reproductive age. Insulin resistance is a main pathophysiologic feature in these patients. According to some studies, the intake of probiotic bacteria may improve glucose homoeostasis. The aim of this study was to investigate the effect of synbiotics on metabolic parameters and apelin in PCOS patients. This randomised double-blind placebo-controlled trial was conducted on eighty-eight PCOS women aged 19-37 years old...
February 2018: British Journal of Nutrition
Jaime Gallo-Villegas, Juan Carlos Aristizabal, Mauricio Estrada, Luis H Valbuena, Raul Narvaez-Sanchez, Jorge Osorio, Daniel C Aguirre-Acevedo, Juan C Calderón
BACKGROUND: Evidence of the efficacy of high-intensity, low-volume interval training (HIIT-low volume) in treating insulin resistance (IR) in patients with metabolic disorders is contradictory. In addition, it is unknown whether this effect is mediated through muscle endocrine function, which in turn depends on muscle mass and fiber type composition. Our aims were to assess the efficacy of HIIT-low volume compared to continuous aerobic exercise (CAE) in treating IR in adults with metabolic syndrome (MS) and to establish whether musclin, apelin, muscle mass and muscle composition are mediators of the effect...
February 27, 2018: Trials
Edyta Machura, Maria Szczepańska, Elżbieta Świętochowska, Franciszek Halkiewicz, Małgorzata Barć-Czarnecka, Katarzyna Ziora, Dariusz Ziora
INTRODUCTION: Patients with CF present numerous pathological conditions such as malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal glucose metabolism, increased insulin resistance, chronic energy deficit, local and chronic inflammation), which could affect or be associated with altered adipokines concentrationMaterial and Methods: We aimed in this study to investigate the levels of selected adipokines such as resistin, apelin, adiponectin to demonstrate their application as possible markers of inflammation...
February 21, 2018: Endokrynologia Polska
Irina Studneva, Valentin Shulzhenko, Oksana Veselova, Oleg Pisarenko
The maintenance of nitric oxide (NO) bioavailability has been recognized as an important component of myocardial protection during cardiac surgery. This study was designed to evaluate the efficacy of using two NO-donating compounds in cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working rat hearts were subjected to normothermic global ischemia and reperfusion...
February 20, 2018: Journal of Physiology and Biochemistry
Kien Tran, Alexandre Murza, Xavier Sainsily, David Coquerel, Jérôme Côté, Karine Belleville, Lounès Haroune, Jean-Michel Longpré, Robert Dumaine, Dany Salvail, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life > 3 h versus 24 min for Pyr-apelin-13), accompanied with improved affinity (analogue 15, Ki 0...
February 20, 2018: Journal of Medicinal Chemistry
Zhi-Yong Xiao, Bo Wang, Wan Fu, Xin Jin, Yong You, Shao-Wen Tian, Xin Kuang
The peptide apelin and its receptor APJ are found to express in multiple brain regions, especially in the regions such as the hippocampus and hypothalamus that play important roles in stress and depression. The distribution of apelin and APJ suggests that the apelinergic signaling may be a key mediator in the development of stress-related depressive behavior. We recently demonstrated that intracerebroventricular (i.c.v) injection of apelin-13 exerts an antidepressant-like activity in the rat forced swimming test (FST)...
February 9, 2018: Neuroscience
Sulé Gunter, Chanel Robinson, Gavin R Norton, Angela J Woodiwiss, Linda Tsang, Aletta M E Millen, Patrick H Dessein
Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease...
February 8, 2018: Clinical Rheumatology
F P M O'Harte, V Parthsarathy, C Hogg, P R Flatt
Nine structurally modified apelin-13 analogues were assessed for their in vitro and acute in vivo antidiabetic potential. Stability was assessed in mouse plasma and insulinotropic efficacy tested in cultured pancreatic BRIN-BD11 cells and isolated mouse pancreatic islets. Intracellular Ca2+ and cAMP production in BRIN-BD11 cells was determined, as was glucose uptake in 3T3-L1 adipocytes. Acute antihyperglycemic effects of apelin analogues were assessed following i.p. glucose tolerance tests (ipGGT, 18 mmol/kg) in normal and diet-induced-obese (DIO) mice and on food intake in normal mice...
February 2018: Peptides
S Saral, M Alkanat, A Sumer, S Canpolat
In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats...
2018: Bratislavské Lekárske Listy
Rahime Sekerci, Nuray Acar, Filiz Tepekoy, Ismail Ustunel, Nigar Keles-Celik
Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work...
January 29, 2018: Acta Histochemica
Chantal Bertrand, Jean-Philippe Pradère, Nancy Geoffre, Simon Deleruyelle, Bernard Masri, Jean Personnaz, Sophie Le Gonidec, Aurélie Batut, Katie Louche, Cédric Moro, Philippe Valet, Isabelle Castan-Laurell
PURPOSE: Apelin treatment has been shown to improve insulin sensitivity in insulin resistant mice by acting in skeletal muscles. However, the effects of systemic apelin on the hepatic energy metabolism have not been addressed. We thus aimed to determine the effect of chronic apelin treatment on the hepatic lipid metabolism in insulin resistant mice. The apelin receptor (APJ) expression was also studied in this context since its regulation has only been reported in severe liver pathologies...
February 1, 2018: Endocrine
Xiaoting Li, Lu Yu, Jing Gao, Xukun Bi, Juhong Zhang, Shiming Xu, Meihui Wang, Mengmeng Chen, Fuyu Qiu, Guosheng Fu
Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation...
February 2018: Aging and Disease
A Strohbach, M Pennewitz, M Glaubitz, R Palankar, S Groβ, F Lorenz, I Materzok, A Rong, M C Busch, S B Felix, M Delcea, R Busch
The adaption of endothelial cells to local flow conditions is a multifunctional process which leads to distinct alterations in cell shape, the subcellular distribution of structural proteins, and cellular function. G-protein-coupled receptors (GPCRs) have been identified to be fundamentally involved in such processes. Recently, we and others have shown that the expression of the endothelial GPCR apelin receptor (APJ) is regulated by fluid flow and that activation of APJ participates in signaling pathways which are related to processes of mechanotransduction...
January 25, 2018: Journal of Cellular Physiology
Soha M Abd El Dayem, Ahmed A Battah, Abo El Maged El Bohy, Rash Nazih Yousef, Azza M Ahmed, Ahmed A Talaat
AIM: To evaluate the relationship of apelin and nitric oxide (NO) to endothelial dysfunction in type 1 diabetics. PATIENTS AND METHODS: Sixty two type 1 diabetics and 30 healthy age and sex matched controls were included. Blood samples for apelin, NO, glycosylated hemoglobin (HbA1c), and lipid profile were collected. Albumin/creatinine ratio was assessed in urine. Flow mediated dilatation (FMD) via ultrasound was done. RESULTS: The mean age of diabetics were 16...
December 15, 2017: Open Access Macedonian Journal of Medical Sciences
Kyungsoo Shin, Calem Kenward, Jan K Rainey
Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein-coupled receptor named the apelin receptor (AR/APJ/APLNR). Ligand-AR interactions have been implicated in regulation of the adipoinsular axis, cardiovascular system, and central nervous system alongside pathological processes. Each ligand may be processed into a variety of bioactive isoforms endogenously, with apelin ranging from 13 to 55 amino acids and apela from 11 to 32, typically being cleaved C-terminal to dibasic proprotein convertase cleavage sites...
December 12, 2017: Comprehensive Physiology
Parvin Babaei, Adele Dastras, Bahram Soltani Tehrani, Shiva Pourali Roudbaneh
Objectives: Ovarian hormones have been shown to regulate body weight, intra-abdominal fat accumulation and plasma level of cytokines. The aim of this study was to investigate the effect of estrogen replacement therapy on visceral adipose tissue, plasma level of apelin, lipid profiles, and glucose in ovariectomized (OVX) rats. Methods: Thirty female Wistar rats were divided into OVX (n = 20) and sham (n = 10) groups. OVX rats were subdivided into estrogen replacement therapy (OVX+est; n = 10) receiving 17 β-estradiol valerates (30 µg/kg, s...
December 2017: Journal of Menopausal Medicine
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