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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/29330351/the-vegfa165b-isoform-is-dysregulated-in-senescent-endothelial-cells-and-may-be-associated-with-prevalent-and-incident-coronary-heart-disease
#1
Eva Latorre, Luke C Pilling, Benjamin P Lee, Stefania Bandinelli, David Melzer, Luigi Ferrucci, Lorna W Harries
Coronary heart disease (CHD) is a leading cause of morbidity in the over 65s; over 40% of all deaths are due to this condition. The association between increasing age and CHD is well-documented; the accumulation of senescent cells in cardiac and vascular tissues may represent one factor underpinning this observation. We aimed to identify senescence-related expression changes in primary human senescent cardiomyocytes and endothelial cells and to relate transcript expression in peripheral blood leucocytes to prevalent and incident CHD in the InCHIANTI study of aging...
January 12, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29321218/non-uniform-relationship-between-salt-status-and-aldosterone-activity-in-patients-with-chronic-kidney-disease
#2
Alison H M Taylor, Alastair J Rankin, Emily P McQuarrie, E Marie Freel, Natalie Z M Homer, Ruth Andrew, Alan G Jardine, Patrick B Mark
BACKGROUND: Hypertension is prevalent in chronic kidney disease (CKD). Studies suggest that reduction in dietary salt intake reduces blood pressure (BP). We studied relationships between salt intake, BP and renin angiotensin system regulation in order to establish if it is disordered in CKD. METHODS: Mechanistic crossover study of CKD patients versus non-CKD controls. Participants underwent modified saline suppression test prior to randomisation to either low or high salt diet for 5 days and then crossed over to the alternate diet...
January 10, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29295895/impaired-contraction-of-blood-clots-as-a-novel-prothrombotic-mechanism-in-systemic-lupus-erythematosus
#3
Giang Le Minh, Alina D Peshkova, Izabella A Andrianova, Timur B Sibgatullin, Adelia N Maksudova, John W Weisel, Rustem Litvinov
The aim of this work was to examine a possible role of clot contraction/retraction in thrombotic complications of systemic lupus erythematosus (SLE). Using a novel automated method, we investigated kinetics of clot contraction in the blood of 51 SLE patients and 60 healthy donors. The functionality of platelets in the SLE patients was assessed using flow cytometry by expression of P-selectin and fibrinogen-binding capacity. The rate and degree of clot contraction were significantly reduced in SLE patients compared to healthy subjects, especially in the patients with higher blood levels of anti-dsDNA antibodies...
January 2, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29269381/independent-and-combined-effects-of-airway-remodelling-and-allergy-on-airway-responsiveness
#4
Kimberley Cw Wang, Timothy D Le Cras, Alexander N Larcombe, Graeme R Zosky, John G Elliot, Alan L James, Peter B Noble
Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness in asthma, however their interrelationships are unclear. This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. We integrated a protocol of ovalbumin (OVA)-induced allergy into a non-inflammatory mouse model of ASM remodelling induced by conditional and airway-specific expression of TGF-α in Egr-1 deficient transgenic mice, which produced thickening of the ASM layer following ingestion of doxycycline...
December 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29263137/functional-blocking-of-ninjurin1-as-a-strategy-for-protecting-endothelial-cells-in-diabetes-mellitus
#5
Xin Wang, Jinbao Qin, Xing Zhang, Zhiyou Peng, Kaichuang Ye, Xiaoyu Wu, Xinrui Yang, Huihua Shi, Zhen Zhao, Xin Guo, Xiaobing Liu, Minyi Yin, Xinwu Lu
Ongoing efforts to remove pathological inflammatory stimuli are crucial for the protection of endothelial cells in diabetes. Nerve injury-induced protein 1 (Ninj1) is an adhesion molecule that not only contributes to inflammation but also regulates the apoptosis of endothelial cells. In the present study, Ninj1 was found highly expressed in endothelial cells in type 2 diabetic mice and increased in high-glucose (HG) cultured HUVECs. Furthermore, we found that Ninj1 levels are up-regulated in endothelial cells in clinical specimens of diabetic patients when compared with non-diabetic tissues, indicating a biological correlation between Ninj1 and endothelial pathophysiology in diabetic condition...
December 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29263136/fetal-growth-restriction-in-mice-modifies-postnatal-airway-responsiveness-in-an-age-and-sex-dependent-manner
#6
Kimberley C W Wang, Alexander N Larcombe, Luke J Berry, Jude S Morton, Sandra T Davidge, Alan L James, Peter B Noble
Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma, however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.5 and then returned to normoxic conditions for the remainder of pregnancy. A control group were housed under normoxic conditions throughout pregnancy...
December 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29237724/dual-%C3%AE-v%C3%AE-3-and-%C3%AE-v%C3%AE-5-blockade-attenuates-fibrotic-and-vascular-alterations-in-a-murine-model-of-systemic-sclerosis
#7
Gianluca Bagnato, Natasha Irrera, Gabriele Pizzino, Domenico Santoro, William Neal Roberts, Gianfilippo Bagnato, Giovanni Pallio, Mario Vaccaro, Francesco Squadrito, Antonino Saitta, Domenica Altavilla, Alessandra Bitto
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibroblast activation and fibrosis of the skin and internal organs. Alterations in cell-integrin interaction are sufficient to initiate pro-fibrotic processes. SSc fibroblasts express both αvβ3 and αvβ5 integrins and their activation induces myofibroblasts differentiation. The aim of this study was to evaluate the effect of the anb3 and anb5 inhibitor, cilengitide, on the development of vascular and fibrotic changes in the chronic oxidant stress murine model of systemic sclerosis...
December 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29229868/sex-dependent-differences-in-inflammatory-responses-during-liver-regeneration-in-a-murine-model-of-acute-liver-injury
#8
Debora Bizzaro, Marika Crescenzi, Rosa Di Liddo, Diletta Arcidiacono, Andrea Cappon, Thomas Bertalot, Vincenzo Amodio, Alessia Tasso, Annalisa Stefani, Valentina Bertazzo, Giacomo Germani, Chiara Frasson, Giuseppe Basso, Pierpaolo Parnigotto, Malcolm Ronald Alison, Patrizia Burra, Maria Teresa Conconi, Francesco Paolo Russo
A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and sacrificed after 3, 5 and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide...
December 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29222092/targeted-disruption-of-the-kcnj5-gene-in-the-female-mouse-lowers-aldosterone-levels
#9
Iris Hardege, Lu Long, Raya Al Maskari, Nicola Figg, Kevin M O'Shaughnessy
Aldosterone is released from adrenal zona glomerulosa cells and plays an important role in Na and K homeostasis. Mutations in the human KCNJ5 gene encoding the GIRK4 potassium channel cause abnormal aldosterone secretion and hypertension. To better understand the role of wild-type (WT) GIRK4 in regulating aldosterone release we have looked at aldosterone secretion in a Kcnj5 knock-out (KO) mouse.  We found that female, but not male, KO mice have reduced aldosterone levels compared to WT female controls, but higher levels of aldosterone after Ang-II stimulation...
December 8, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29212786/endoplasmic%C3%A2-reticulum%C3%A2-stress-autophagy%C3%A2-pathway%C3%A2-is%C3%A2-involved%C3%A2-in-diabetes-induced-neuronal%C3%A2-apoptosis%C3%A2-and-cognitive%C3%A2-decline%C3%A2-in%C3%A2-mice
#10
Fei-Juan Kong, Lei-Lei Ma, Jun-Jie Guo, Lin-Hao Xu, Yun Li, Shen Qu
Diabetes mellitus is a significant global public health problem depicting a rising prevalence worldwide. As a serious complication of diabetes, diabetes-associated cognitive decline is attracting increasing attention. However, the underlying mechanisms are yet to be fully determined. Both endoplasmic reticulum (ER) stress and autophagy have been reported to modulate neuronal survival and death and be associated with several neurodegenerative diseases...
December 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29187513/a-critical-evaluation-of-the-anabolic-response-after-bolus-or-continuous-feeding-in-copd-and-healthy-older-adults
#11
Renate Jonker, Nicolaas Ep Deutz, Rajesh Harrykissoon, Anthony J Zachria, Eugene A Veley, Mariëlle Pkj Engelen
After bolus and continuous enteral feeding of the same protein, different digestion and absorption kinetics and anabolic responses are observed. Establishing which mode of feeding has the highest anabolic potential in patients with chronic obstructive pulmonary disease (COPD) may aid in the prevention of muscle wasting, but an important confounding factor is the duration of assessments after bolus feeding. We hypothesized that the anabolic response to bolus and continuous feeding in COPD patients is comparable when methodological issues are addressed...
November 29, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29175946/hypertrophied-myocardium-is-vulnerable-to-ischemia-reperfusion-injury-and-refractory-to-rapamycin-induced-protection-due-to-increased-oxidative-nitrative-stress
#12
Lei-Lei Ma, Pei-Pei Yin, Yang Li, Fei-Juan Kong, Jun-Jie Guo, Hong-Tao Shi, Jian-Bin Zhu, Yun-Zeng Zou, Jun-Bo Ge
Left ventricular hypertrophy (LVH) is causally related to increased morbidity and mortality following acute myocardial infarction (AMI) via still unknown mechanisms. Although rapamycin exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited cardioprotection are altered in the presence of LVH has yet to be determined. Pressure overload-induced cardiac hypertrophied mice and sham-operated controls were exposed to AMI by coronary artery ligation, and treated with vehicle or rapamycin  10 min before reperfusion...
November 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#13
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
AIMS/HYPOTHESIS: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. This study aimed at evaluating whether TRAIL had the potential to treat type 2 diabetes. METHODS: Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
November 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29167317/rodent-vertical-sleeve-gastrectomy-alters-maternal-immune-health-and-feto-placental-development
#14
Redin A Spann, Wiiliam J Lawson, Gene L Bidwell, C Austin Zamarripa, Rodrigo O Maranon, Sibali Bandyopadhyay, Erin R Taylor, Jane F Reckelhoff, Michael R Garrett, Bernadette E Grayson
Bariatric surgery is increasingly employed to improve fertility and reduce obesity related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy...
November 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29162746/vascular-dysfunction-in-the-stroke-prone-spontaneously-hypertensive-rat-is-dependent-on-constrictor-prostanoid-activity-and-y-chromosome-lineage
#15
Shanzana I Khan, Karen L Andrews, Ann-Maree Jefferis, Garry L Jennings, Amanda K Sampson, Jaye P F Chin-Dusting
Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to-date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to-date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here we show that vascular dysfunction in the SHRSP is attributable to differential cyclo-oxygenase (COX) activity with NO levels playing a less significant role...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29162745/does-sympathetic-dysfunction-occur-before-denervation-in-pure-autonomic-failure
#16
Ling Guo, Murray D Esler, Carolina Sari, Sarah Phillips, Elisabeth A Lambert, Nora E Straznicky, Gavin W Lambert, Susan J Corcoran
BACKGROUND: Pure autonomic failure (PAF) is a rare sporadic disorder characterised by autonomic failure in the absence of a movement disorder or dementia and is associated with very low plasma norepinephrine levels - suggesting widespread sympathetic denervation, however the underlying pathology remains poorly elucidated. We sought to correlate clinical and neurochemical findings with sympathetic nerve protein abundances, accessed by way of a forearm vein biopsy, in patients with PAF and in healthy controls and patients with multiple systems atrophy (MSA) in whom sympathetic nerves are considered intact...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29122967/hepatic-accumulation-of-s-adenosylmethionine-in-hamsters-with-non-alcoholic-fatty-liver-disease-associated-to-metabolic-syndrome-under-selenium-and-vitamin-e-deficiency
#17
Josep M Del Bas, Benjamín Rodríguez, Francesc Puiggròs, Silvia Mariné, Miguel Angel Rodríguez, David Moriña, Lluís Armengol, Antoni Caimari, Lluís Arola
Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT...
November 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29109300/the-shifted-balance-between-circulating-follicular-regulatory-t-cells-and-follicular-helper-t-cells-in-patients-with-ulcerative-colitis
#18
Xinrui Wang, Yonggang Zhu, Manli Zhang, Jie Hou, Hongjuan Wang, Yanfang Jiang, Haifeng Wang, Pujun Gao
B cell immunity participates in the pathogenesis of ulcerative colitis (UC). The immune balance between follicular regulatory T (TFR) cells and follicular helper T (TFH) cells is important in regulating B cell responses. However, the alteration of TFR/TFH balance in UC remains unclear. Peripheral blood from 25 UC patients and 15 healthy controls was examined for the frequencies of circulating TFR, TFH, and regulatory T (Treg) cells by flow cytometry. Levels of serum cytokines were measured using cytometric bead array (CBA)...
November 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29101299/relaxin-contributes-to-the-regulation-of-arterial-pressure-in-adult-female-mice
#19
Katrina M Mirabito Colafella, Chrishan S Samuel, Kate M Denton
Relaxin is increasingly being recognized as a potent vasodilatory and anti-fibrotic hormone. Given that relaxin is present in the circulation during luteal phase of the menstrual cycle and during pregnancy, when arterial pressure is lowest in women, relaxin may contribute to the relative cardiovascular protection observed in premenopausal women as compared to age-matched men and post-menopausal women. In the present study, we investigated the contribution of relaxin to the normal regulation of arterial pressure in adult female and male mice and during pregnancy...
November 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29101298/loss-of-microrna-22-prevents-high-fat-diet-induced-dyslipidemia-and-increases-energy-expenditure-without-affecting-cardiac-hypertrophy
#20
Gabriela Placoná Diniz, Zhan-Peng Huang, Jianming Liu, Jinghai Chen, Jian Ding, Renata Inzinna Fonseca, Maria Luiza Barreto-Chaves, Jose Donato, Xiaoyun Hu, Da-Zhi Wang
Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In this study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected...
November 3, 2017: Clinical Science (1979-)
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