Metabolic disturbances of non-alcoholic fatty liver resemble the alterations typical for type 2 diabetes
We examined metabolic perturbations in people with NAFL, patients with T2DM and people with normal intrahepatic lipid (IHL) (CON). A 2-step (10mU/m2/min, 40mU/m2/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM and 11 CON, all matched for BMI and aerobic fitness. IHL was measured using proton magnetic resonance spectroscopy. Because of high IHL variability in T2DM patients, this group was separated into a high IHL (IHL≥5.0%, T2DM+NAFL) and a normal IHL (IHL
Source: Clinical Science - June 15, 2017 Category: Biomedical Science Authors: Brouwers, B., Schrauwen-Hinderling, V. B., Jelenik, T., Gemmink, A., Havekes, B., Bruls, Y., Dahlmans, D., Roden, M., Hesselink, M. K. C., Schrauwen, P. Tags: PublishAheadOfPrint Source Type: research

Improvement in exercise duration, lung function and well-being in G551D-Cystic Fibrosis patients: a double-blind, placebo-controlled, randomised, cross-over study with ivacaftor
G551D , a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in cystic fibrosis (CF) is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiolo...
Source: Clinical Science - June 13, 2017 Category: Biomedical Science Authors: Keating, D. T., Edgeworth, D., Ellis, M., Button, B., Williams, E., Clark, D., Tierney, A., Heritier, S., Kotsimbos, A., Wilson, J. Tags: PublishAheadOfPrint Source Type: research

Quantification of Circulating GDF-11 and {beta}2-MG in Aged Patients with Age-related Impairment in Cognitive Function
Conclusion: Our results suggest that circulating GDF-11 may not exert a protective effect during the aging process or on cognitive function, and β2-MG may play a role in ageing and cognitive impairment. However, it is possible that the relatively small sample size in this study affected the quality of the statistical analysis, and future studies are needed to further validate our findings. (Source: Clinical Science)
Source: Clinical Science - June 13, 2017 Category: Biomedical Science Authors: Yang, R., Fu, S., Zhao, L., Zhen, B., Ye, L., Niu, X., Li, X., Zhang, P., Bai, J. Tags: PublishAheadOfPrint Source Type: research

Urinary glycated uromodulin in diabetic kidney disease
Advanced glycation end products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD) but non-DM, and no DM patients with normal renal function or healthy control participants; a find...
Source: Clinical Science - June 7, 2017 Category: Biomedical Science Authors: Chang, C.-C., Chen, C.-Y., Huang, C.-H., Wu, C.-L., Wu, H.-M., Chiu, P.-F., Kor, C.-T., Chen, T.-H., Chang, G.-D., Kuo, C.-C., Wen, H.-C., Huang, C.-Y., Chang, C.-H. Tags: PublishAheadOfPrint Source Type: research

Mycobacterium tuberculosis Rv3615c is a highly immunodominant antigen and specifically induces potent Th1-type immune responses in tuberculosis pleurisy
T-cell responses have been demonstrated essential for preventing M .tb infection. The Th1-cytokines produced by T cells, such as INF-, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity. Here, we studied human pulmonary T-cell responses induced by M.tb -specific antigen Rv3615c, a protein with a s...
Source: Clinical Science - June 6, 2017 Category: Biomedical Science Authors: Li, J., Shen, J., Lao, S., Li, X., Liu, J., Wu, C. Tags: PublishAheadOfPrint Source Type: research

ABCB1 gene polymorphism associated with clinical factors can predict drug-resistant tuberculosis
Polymorphism in ABCB1 gene encoding P-glycoprotein, a transmembrane drug efflux pump, contributes to drug resistance and have been widely studied, however, their association with rifampicin and ethambutol resistance in tuberculosis patients are still unclear. Genotype/allele/haplotype frequencies in c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) were obtained from 212 patients, of these, 80 patients with rifampicin and/or ethambutol resistance were selected as case group and 132 control-group through the result of their culture and drugs sensitive test. Patients aging ABCB1 polymorphisms ...
Source: Clinical Science - June 1, 2017 Category: Biomedical Science Authors: Pontual, Y., Pacheco, V. d. S. d. S., Monteiro, S. P., Quintana, M. S. B., Costa, M. J. M., Rolla, V. C., De Castro, L. Tags: PublishAheadOfPrint Source Type: research

Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy
In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia. (Source: Clinical Science)
Source: Clinical Science - May 31, 2017 Category: Biomedical Science Authors: Huda, S., Jordan, F., Bray, J., Love, G., Payne, R., Sattar, N., Freeman, D. J. Tags: PublishAheadOfPrint Source Type: research

Smad7 protects against Acute Kidney Injury by rescuing tubular epithelial cells from the G1 cell cycle arrest
In conclusion, Smad7 plays a protective role in AKI. Blockade of TGF-β/Smad3-p21/p27-induced G1 cell cycle arrest may be a key mechanism by which Smad7 treatment inhibits AKI. Thus, Smad7 may be a novel therapeutic agent for AKI. (Source: Clinical Science)
Source: Clinical Science - May 31, 2017 Category: Biomedical Science Authors: Fu, S., Tang, Y., Huang, X. R., Feng, M., Xu, A., Lan, H. Y. Tags: PublishAheadOfPrint Source Type: research

FGF21 ameliorates diabetic cardiomyopathy by activating the AMPK-paraoxonase 1 signaling axis in mice
Conclusion: These findings suggest that FGF21 ameliorates diabetic cardiomyopathy in part by activation of the AMPK-PON1 axis. (Source: Clinical Science)
Source: Clinical Science - May 30, 2017 Category: Biomedical Science Authors: Wu, F., Wang, B., Zhang, S., Shi, L., Wang, Y., Xiong, R., Pan, X., Gong, F., Li, X., Lin, Z. Tags: PublishAheadOfPrint Source Type: research

Exacerbation of oxygen-glucose deprivation-induced blood brain barrier disruption: potential pathogenic role of interleukin 9 in ischemic stroke
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood brain barrier (BBB) foll...
Source: Clinical Science - May 26, 2017 Category: Biomedical Science Authors: Tan, S., Shan, Y., Wang, Y., Lin, Y., Liao, S., Deng, Z., Zhou, L., Cai, W., Zeng, Q., Zhang, L., Zhang, B., Men, X., Li, H., Hu, X., Wu, C., Peng, L., Lu, Z. Tags: PublishAheadOfPrint Source Type: research

Dynamic response to initial stage blindness in visual system development
Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity when facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting 2 to 8 mon...
Source: Clinical Science - May 24, 2017 Category: Biomedical Science Authors: Long, E., Zhang, X., Liu, Z., Wu, X., Tan, X., Lin, D., Cao, Q., Chen, J., Lin, Z., Wang, D., Li, X., Li, J., Wang, J., Li, W., Lin, H., Chen, W., Liu, Y. Tags: PublishAheadOfPrint Source Type: research

Peroxisome proliferator-activated receptor {gamma} agonism attenuates endotoxaemia induced muscle protein loss and lactate accumulation in rats
We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg.kg-1.day-1) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg.kg-1.h-1) or saline. Rosi blunted LPS-induced increases in muscle tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% ( P
Source: Clinical Science - May 23, 2017 Category: Biomedical Science Authors: Crossland, H., Constantin-Teodosiu, D., Gardiner, S., Greenhaff, P. Tags: PublishAheadOfPrint Source Type: research

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway
This study indicates the potential application of HDAC3 inhibitor for the prevention of DCM. (Source: Clinical Science)
Source: Clinical Science - May 22, 2017 Category: Biomedical Science Authors: Xu, Z., Tong, Q., Zhang, Z., Wang, S., Zheng, Y., Liu, Q., Qian, L., Chen, S.-y., Sun, J., Cai, L. Tags: PublishAheadOfPrint Source Type: research

Endothelial Nox1 Oxidase Assembly in Human Pulmonary Arterial Hypertension; Driver of Gremlin1-Mediated Proliferation
Conclusion: Together these data support a Nox1-Gremlin1 signaling axis in pulmonary vascular endothelium that is likely to contribute to pathophysiological endothelial proliferation and the progression of PAH. The findings also support targeting of Nox1 as a viable therapeutic option to combat PAH. (Source: Clinical Science)
Source: Clinical Science - May 18, 2017 Category: Biomedical Science Authors: Al Ghouleh, I., Sahoo, S., Meijles, D. N., Amaral, J. H., de Jesus, D. S., Sembrat, J., Rojas, M., Goncharov, D. A., Goncharova, E. A., Pagano, P. J. Tags: PublishAheadOfPrint Source Type: research

Pulse-wave velocity is associated with cognitive impairment in hemodialysis patients
Conclusions: High prevalence of cognitive impairment in hemodialysis patients was confirmed. For the first time, an association between cognitive impairment and arterial stiffness was detected in a larger cohort of hemodialysis patients. Concerning the underlying pathogenesis of cognitive impairment, current results revealed a potential involvement of arterial stiffness, which has to be further evaluated in future studies. (Source: Clinical Science)
Source: Clinical Science - May 11, 2017 Category: Biomedical Science Authors: Angermann, S., Baumann, M., Wassertheurer, S., Mayer, C. C., Steubl, D., Hauser, C., Suttmann, Y., Reichelt, A.-L., Satanovskij, R., Lorenz, G., Lukas, M., Haller, B., Heemann, U., Grimmer, T., Schmaderer, C. Tags: PublishAheadOfPrint Source Type: research

Oxidative imbalance and kidney damage in spontaneously hypertensive rats: activation of extrinsic apoptotic pathway
We examined plasmatic pro-oxidant and antioxidant status showing a significant alteration in oxidative balance in SHR. As index of oxidative damage, we evaluated lipid peroxidation in kidney, liver and skeletal muscle, detecting a significant rise in lipid peroxidation levels in all SHR tissues, particularly relevant in kidney. In addition, we analyzed the expression of cytoplasmic antioxidant enzymes, SOD1 and GSTP1. In SHR liver, SOD1 expression slight increased while we have not detected any variation in other tissues. Concerning GSTP1, SHR renal tissues did not display variations in enzyme expression, while, in the oth...
Source: Clinical Science - May 11, 2017 Category: Biomedical Science Authors: La Russa, D., Brunelli, E., Pellegrino, D. Tags: PublishAheadOfPrint Source Type: research

Phosphoinositide 3-Kinase (p110{alpha}) Gene Delivery Limits Diabetes-induced Cardiac NADPH Oxidase and Cardiomyopathy in a Mouse Model with Established Diastolic Dysfunction
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterised by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the current study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to...
Source: Clinical Science - May 9, 2017 Category: Biomedical Science Authors: Prakoso, D., DeBlasio, M. J., Qin, C., Rosli, S., Kiriazis, H., Qian, H., Du, X.-J., Weeks, K. L., Gregorevic, P., McMullen, J. R., Ritchie, R. H. Tags: PublishAheadOfPrint Source Type: research

Discrepant Effects of Heart Failure on Electrophysiological Property in Right Ventricular Outflow Tract and Left Ventricular Outflow Tract Cardiomyocytes
In conclusion, RVOT and LVOT cardiomyocytes had distinctive electrophysiological characteristics. HF differentially modulates AP morphology and ionic currents in RVOT and LVOT cardiomyocytes. (Source: Clinical Science)
Source: Clinical Science - May 9, 2017 Category: Biomedical Science Authors: Lu, Y.-Y., Cheng, C.-C., Tsai, C.-F., Lin, Y. K., Lee, T.-I., Chen, Y.-C., Chen, S.-A., Chen, Y. J. Tags: PublishAheadOfPrint Source Type: research

Using DTI to assess white matter microstructure in Cerebral Small Vessel Disease (SVD) in multi-centre studies
This study supports the use of DTI metrics as biomarkers of disease progression in multi-centre studies. (Source: Clinical Science)
Source: Clinical Science - May 9, 2017 Category: Biomedical Science Authors: Croall, I. D., Lohner, V., Moynihan, B., Khan, U., Hassan, A., O'Brien, J. T., Morris, R. G., Tozer, D. J., Cambridge, V. C., Harkness, K., Werring, D., Blamire, A. M., Ford, G. A., Barrick, T. R., Markus, H. S. Tags: PublishAheadOfPrint Source Type: research

High phosphate induces a pro-inflammatory response by vascular smooth muscle cells. Modulation by vitamin D derivatives
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3.3 mM) medium caused an increased expression of the pro-inflammatory mediators ICAM-1, IL-1β, IL-6, IL...
Source: Clinical Science - May 3, 2017 Category: Biomedical Science Authors: Martinez-Moreno, J. M., Herencia, C., Montes de Oca, A., Diaz-Tocados, J. M., Vergara, N., Gomez, M. J., Lopez-Arguello, S. D., Camargo, A., Peralbo-Santaella, E., Rodriguez-Ortiz, M. E., CANALEJO, A., Rodriguez, M., Munoz-Castaneda, J. R., Almaden, Y. Tags: PublishAheadOfPrint Source Type: research

Reliability of an automatic classifier for brain enlarged perivascular spaces burden and comparison with human performance
In the brain, enlarged perivascular spaces (PVS) relate to cerebral small vessel disease, poor cognition, inflammation and hypertension. We propose a fully automatic scheme that uses a support vector machine(SVM) to classify the burden of PVS in the basal ganglia(BG) region as low or high. We assess the performance of three different types of descriptors extracted from the BG region in T2-weighted MRI images: 1)statistics obtained from Wavelet transform's coefficients, 2)local binary patterns and 3)bag of visual words (BoW)-based descriptors characterising local keypoints obtained from a dense grid with the scale-invariant...
Source: Clinical Science - May 3, 2017 Category: Biomedical Science Authors: Gonzalez-Castro, V., Valdes-Hernandez, M. d. C., chappell, f., Armitage, P. A., Makin, S., Wardlaw, J. Tags: PublishAheadOfPrint Source Type: research

Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in nonalcoholic fatty liver disease
Conclusions: IR favors fibrosis deposition independently of the classic "inflammation - HSC trans-differentiation" pathway. The mechanism entails a cross-talk between enhanced lipotoxicity in insulin resistant hepatocytes and Loxl2 production by HSCs, which was confirmed in patients with diabetes, thereby facilitating extracellular matrix stabilization. (Source: Clinical Science)
Source: Clinical Science - May 3, 2017 Category: Biomedical Science Authors: Dongiovanni, P., Meroni, M., Baselli, G. A., Bassani, G. A., Rametta, R., Pietrelli, A., Maggioni, M., Facciotti, F., Trunzo, V., Badiali, S., Fargion, S., Gatti, S., Valenti, L. V. C. Tags: PublishAheadOfPrint Source Type: research

ER-stress-dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection
In conclusion, our study demonstrated that elevated mechanical stretch induced MPs formation in SMCs leading to endothelial dysfunction, which is ER stress-dependent. ER stress inhibition suppressed ECs apoptosis, inflammation in aorta and TAAD development. (Source: Clinical Science)
Source: Clinical Science - May 3, 2017 Category: Biomedical Science Authors: Jia, L., Zhang, W.-M., Li, T.-T., Liu, Y., Piao, C.-M., Ma, Y.-C., Lu, Y., Wang, Y., Liu, T.-T., Qi, Y.-F., Du, J. Tags: PublishAheadOfPrint Source Type: research

High phosphate induces a pro-inflammatory response by vascular smooth muscle cells. Modulation by vitamin D derivatives
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3.3 mM) medium caused an increased expression of the pro-inflammatory mediators ICAM-1, IL-1β, IL-6, IL...
Source: Clinical Science - April 25, 2017 Category: Biomedical Science Authors: Martinez-Moreno, J. M., Herencia, C., Montes de Oca, A., Diaz-Tocados, J. M., Vergara, N., Gomez, M. J., Lopez-Arguello, S. D., Camargo, A., Peralbo-Santaella, E., Rodriguez-Ortiz, M. E., CANALEJO, A., Rodriguez, M., Munoz-Castaneda, J. J., Yolanda Almade Tags: PublishAheadOfPrint Source Type: research

DJ-1 overexpression restores ischaemic post-conditioning-mediated cardioprotection in diabetic rats:role of autophagy
IPO (Ischaemic post-conditioning) is a promising method of alleviating myocardial IR (ischaemia -reperfusion) injury; however, IPO-mediated cardioprotection is lost in diabetic hearts via mechanisms that remain largely unclear. We hypothesized that decreased cardiac expression of DJ-1, a positive modulator of autophagy, compromises the effectiveness of IPO-induced cardioprotection in diabetic rats. Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion followed by 120 min of reperfusion) exhibited more severe myocardial injury, less cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monopho...
Source: Clinical Science - April 20, 2017 Category: Biomedical Science Authors: Zhou, B., Lei, S., Xue, R., Leng, Y., Xia, Z., Xia, Z.-y. Tags: PublishAheadOfPrint Source Type: research

Skin-derived precursors from human subjects with type-2 diabetes yield dysfunctional vascular smooth muscle cells.
Objective: Few methods enable molecular and cellular studies of vascular aging or type-2 diabetes (T2D). Here we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and Results: Skin-derived precursors (SKPs) were cultured from biopsies (N=164, ~1 cm2) taken from the edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7±13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield).  The number of SKPs isolated from subjects with ...
Source: Clinical Science - April 19, 2017 Category: Biomedical Science Authors: Steinbach, S. K., Yau, T. M., Ouzounian, M., Abdel-Qadir, H., Chandy, M., Waddell, T., Husain, M. Tags: PublishAheadOfPrint Source Type: research

The association between etanercept serum concentration and psoriasis severity is highly age-dependent
The association between etanercept serum concentration and psoriasis disease severity is poorly investigated and currently etanercept serum concentration monitoring aiming to optimize psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations w...
Source: Clinical Science - April 18, 2017 Category: Biomedical Science Authors: Detrez, I., Van Steen, K., Segaert, S., Gils, A. Tags: PublishAheadOfPrint Source Type: research

DJ-1 overexpression restores ischaemic post-conditioning-mediated cardioprotection in diabetic rats:role of autophagy
IPO (Ischaemic post-conditioning) is a promising method of alleviating myocardial IR (ischaemia -reperfusion) injury; however, IPO-mediated cardioprotection is lost in diabetic hearts via mechanisms that remain largely unclear. We hypothesized that decreased cardiac expression of DJ-1, a positive modulator of autophagy, compromises the effectiveness of IPO-induced cardioprotection in diabetic rats. Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion followed by 120 min of reperfusion) exhibited more severe myocardial injury, less cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monopho...
Source: Clinical Science - April 12, 2017 Category: Biomedical Science Authors: Zhou, B., Lei, S., Xue, R., Leng, Y., Xia, Z., Xia, Z.-y. Tags: PublishAheadOfPrint Source Type: research

High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency promotes angiotensin-II induced aneurysm in mice
In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho -0.129, P=0.033 ). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR 0.40; 95% CI, 0.19-0.84, P=0.016 , adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared to the relatively normal AAA neck. To further assess the role of TSP-1 in AAA progression, combi...
Source: Clinical Science - April 6, 2017 Category: Biomedical Science Authors: Krishna, S. M., seto, S., Jose, R., Li, J., Moxon, J. V., Clancy, P., Crossman, D. J., Norman, P. E., Emeto, T. I., Golledge, J. Tags: PublishAheadOfPrint Source Type: research

Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction
In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function. (Source: Clinical Science)
Source: Clinical Science - April 6, 2017 Category: Biomedical Science Authors: Morishima, T., Restaino, R. M., Walsh, L. K., Kanaley, J. A., Padilla, J. Tags: PublishAheadOfPrint Source Type: research

Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease
This study suggests that elevated NGAL promotes COPD airway remodelling possibly through altered EMT. NGAL may be a potential target for reversing airway obstruction and remodelling in COPD. (Source: Clinical Science)
Source: Clinical Science - April 5, 2017 Category: Biomedical Science Authors: Wang, Y., Jia, M., Yan, X., Cao, L., Barnes, P. J., Adcock, I. M., Huang, M., Yao, X. Tags: PublishAheadOfPrint Source Type: research

High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency promotes angiotensin-II induced aneurysm in mice
In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho -0.129, P=0.033 ). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR 0.40; 95% CI, 0.19-0.84, P=0.016 , adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared to the relatively normal AAA neck. To further assess the role of TSP-1 in AAA progression, combi...
Source: Clinical Science - March 31, 2017 Category: Biomedical Science Authors: Krishna, S., seto, S., Jose, R., Li, J., Moxon, J. V., Clancy, P., Crossman, D. J., Norman, P. E., Emeto, T. I., Golledge, J. Tags: PublishAheadOfPrint Source Type: research

Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery
Recently, H2O2 has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and besides NO, generates H2O2. The role of nNOS-derived H2O2 in human vessels is so far unknown. The present study aimed at investigating the relevance of nNOS/H2O2 signaling in human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting. In IMA, but not in SV, ACh-induced vasod...
Source: Clinical Science - March 30, 2017 Category: Biomedical Science Authors: Endlich, P. W., Aires, R. D., Goncalves, R. L., Costa, E. D., Angelo, J. d. P. A., Alves, L. F., Silva, R. F. d., Rezende, B. A., Cortes, S. F., Lemos, V. S. Tags: PublishAheadOfPrint Source Type: research

A role for Galectin-3 in the development of early molecular alterations in short-term aortic stenosis
Aortic stenosis (AS) is characterized by pressure overload and causes left ventricular (LV) fibrosis and inflammation, two mechanisms which finally lead to cardiac dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin, promotes cardiac remodeling. We herein investigated the role of Gal-3 in LV remodeling in patients with AS and the effects of Gal-3 blockade in rats subjected to short-term (6-week) supravalvular aortic banding (AS group). Myocardial biopsies were obtained from 25 patients with severe AS referred for aortic valve replacement and from necropsies of 11 cardiovascular disease-free contr...
Source: Clinical Science - March 30, 2017 Category: Biomedical Science Authors: Arrieta, V., Martinez-Martinez, E., Ibarrola, J., Alvarez, V., Sadaba, R. J., Garcia-Pena, A., Fernandez-Celis, A., Cachofeiro, V., Rossignol, P., Lopez-Andres, N. Tags: PublishAheadOfPrint Source Type: research

Vascular basement membrane alterations and {beta}-amyloid accumulations in an animal model of cerebral small vessel disease
Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated by the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analysed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks 1) the percentage area immunostained for vascular collagen IV and laminin was quantified, 2) the capillary BM thi...
Source: Clinical Science - March 27, 2017 Category: Biomedical Science Authors: Held, F., Morris, A. W. J., Pirici, D., Niklass, S., Sharp, M. M. G., Garz, C., Assmann, A., Heinze, H.-J., Schreiber, F., Carare, R. O., Schreiber, S. Tags: PublishAheadOfPrint Source Type: research

Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats
In this study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) . Repeated microaspiration of CDCA, DCA and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial-mesenchymal transition (EMT), as indicated by upregulation of  mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, as well as downregulaton of epithelial marker...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: chen, B., You, W. J., Liu, X. Q., Xue, S., Qin, H., Jiang, H. D. Tags: PublishAheadOfPrint Source Type: research

The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression
In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: Wang, K., Song, Y., Liu, W., Wu, X., Zhang, Y., Li, S., Kang, L., Tu, J., Zhao, k., Hua, W., Yang, C. Tags: PublishAheadOfPrint Source Type: research

Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina
Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and RPE-choroid respectively. Vascular endothelial growth factor-A (VEGF), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR. VEGF-A can be alternatively spliced at exon 8 to form 2 families of isoforms, pro- and anti-angiogenic. VEGF-A165a is the most abundant pro-angiogenic isoform, is pro-inflammatory a...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: Ved, N., Hulse, R. P., Bestall, S. M., Donaldson, L. F., Bainbridge, J. W., Bates, D. Tags: PublishAheadOfPrint Source Type: research

Pretreatment with ALDH2 agonist Alda-1 reduces intestinal injury induced by ischemia and reperfusion in mice
This study was to determine whether ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut IR. In a mice model of intestinal IR injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-HNE and MDA were evaluated. The results indicated that IR treatment conferred elevation in pathological scores, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine levels, accompanied by accumulated 4-HNE and MDA. No significant changes in ALDH2 activity were observed after IR. However, Alda-1 pretreatment significantly decreased th...
Source: Clinical Science - March 21, 2017 Category: Biomedical Science Authors: Zhu, Q., He, G., Wang, J., Wang, Y., Chen, W. Tags: PublishAheadOfPrint Source Type: research

Diabetes confers in vitro calcific potential on serum which associates with in-vivo vascular calcification
Although vascular calcification (VC) is prevalent in type 2 diabetes (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) to serum, enabling it to induce VC outside the disease milieu. We therefore investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 45 age- and sex-matched patients with T2DM with MDRD-eGFR>60mL min-1 were analysed for CP using rat aortic smooth muscle cells in vitro . CT scans of femoral arteries identified individuals with in vivo calcification. Serum from subjects ...
Source: Clinical Science - March 20, 2017 Category: Biomedical Science Authors: Patidar, A., Singh, D. K., Thakur, S., Winocour, P., Farrington, K., Baydoun, A. Tags: PublishAheadOfPrint Source Type: research

Downregulation of miR-15a/b accelerates fibrotic remodelling in the type-2 diabetic human and mouse heart
Conclusion: Our results provide first evidence that early downregulation of miR-15a/b activates fibrotic signaling in diabetic heart, hence could be a potential target for the treatment/prevention of diabetes induced fibrotic remodelling of the heart. (Source: Clinical Science)
Source: Clinical Science - March 13, 2017 Category: Biomedical Science Authors: Rawal, S., Munasinghe, P. E., Thevakar, P., Lew, J. K. S., Jones, G. T., Willams, M. J., Davis, P., Bunton, R. W., Galvin, I. F., Manning, P., Lamberts, R. R., Katare, R. G. Tags: PublishAheadOfPrint Source Type: research

Sympathetic nervous activity in patients with Acute Coronary Syndrome: A comparative study of inflammatory biomarkers
Previous studies have shown that both sympathetic hyperactivity and enhanced inflammatory responses are associated with poor outcomes in patients with acute coronary syndrome (ACS). Whether there is a correlation between these two characteristics remains unclear. Thirty-four patients with uncomplicated ACS were evaluated; their mean age was 51.7 ± 7.0 years, 79.4% were male, and 94.1% had myocardial infarction. On the fourth day of hospitalization, they underwent muscle sympathetic nerve activity (MSNA) analysis (microneurography), as well as ultrasensitive C-reactive protein (usCRP), interleukin-6 (IL-6) and l...
Source: Clinical Science - March 13, 2017 Category: Biomedical Science Authors: Moreira, H. G., Lage, R. L., Martinez, D. G., Ferreira-Santos, L., Rondon, M. U. P. B., Negrao, C. E., Nicolau, J. C. Tags: PublishAheadOfPrint Source Type: research

Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats.
Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor p66Shc-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, Pin1, in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intrape...
Source: Clinical Science - March 1, 2017 Category: Biomedical Science Authors: Feng, D., Yao, J., Wang, G., Li, Z., Zu, G., Li, Y., Luo, F., Ning, S., Qasim, W., Chen, Z., Tian, X. Tags: PublishAheadOfPrint Source Type: research

Synergistic effects of citrulline supplementation and exercise on performance in male rats: evidences for implication of protein and energy metabolisms
Background: Exercise and citrulline are both regulators of muscle protein metabolism. However, the combination of both has been under-studied yet may have synergistic effects on muscle metabolism and performance. Methods: Three-month-old healthy male rats were randomly assigned to be fed ad libitum for 4 weeks with either a citrulline-enriched diet (1g/kg/day) ( CIT ) or an isonitrogenous standard diet (by addition of nonessential amino acid) ( Ctrl ) and trained (running on treadmill 5d/wk) ( ex ) or not. Maximal endurance activity and body composition were assessed, and muscle protein metabolism (protein synthesis, prote...
Source: Clinical Science - March 1, 2017 Category: Biomedical Science Authors: Goron, A., Lamarche, F., Cunin, V., Dubouchaud, H., Hourde, C., Noirez, P., Corne, C., Couturier, K., Seve, M., Fontaine, E., Moinard, C. Tags: PublishAheadOfPrint Source Type: research

The effect of cortisol in rat steatotic and non-steatoticliver transplantation from brain-dead donors
This study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. (Source: Clinical Science)
Source: Clinical Science - February 28, 2017 Category: Biomedical Science Authors: Jimenez-Castro, M. B., Negrete-Sanchez, E., Casillas-Ramirez, A., Gulfo, J., Alvarez-Mercado, A. I., Cornide-Petronio, M. E., Gracia-Sancho, J., Rodes, J., Peralta, C. Tags: PublishAheadOfPrint Source Type: research

Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats.
Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor p66Shc-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, Pin1, in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intrape...
Source: Clinical Science - February 23, 2017 Category: Biomedical Science Authors: Tian, X., Feng, D., Yao, J., Wang, G., Li, Z., Zu, G., Li, Y., Luo, F., Ning, S., Qasim, W., Chen, Z. Tags: PublishAheadOfPrint Source Type: research

hDPSCs fabricate a vascularised woven bone tissue: a new tool in bone tissue engineering
Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells successfully used in human bone tissue engineering. To better establish if these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim to obtain a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers and cultured. Growth curves, expression of bone-related markers, calcification, angiogenesis as well as in vivo transplantation assay were performed. We found th...
Source: Clinical Science - February 16, 2017 Category: Biomedical Science Authors: Paino, F., La Noce, M., Giuliani, A., De Rosa, A., Mazzoni, S., Laino, L., Amler, E., papaccio, g., Desiderio, V., Tirino, V. Tags: PublishAheadOfPrint Source Type: research

Simvastatin pre-treatment improves survival and mitochondrial function in a three-day fluid-resuscitated rat model of sepsis.
Statins may offer protective effects in sepsis through anti-inflammatory, mitochondrial protection and other actions. We thus evaluated the effects of simvastatin on survival, organ and mitochondrial function, tissue and plasma ubiquinone levels and liver transcriptomics in a 3-day rat model of sepsis. Comparisons of rat plasma simvastatin and ubiquinone levels were made against levels sampled in blood from patients with acute lung injury (ALI) enrolled into a trial of statin therapy. Animals received simvastatin by gavage either pre- or post-induction of faecal peritonitis. Control septic animals received vehicle alone. 7...
Source: Clinical Science - February 15, 2017 Category: Biomedical Science Authors: Morel, J., Hargreaves, I., Brealey, D., Neergheen, V., Backman, J. T., Lindig, S., Blass, M., Bauer, M., McAuley, D. F., Singer, M. Tags: PublishAheadOfPrint Source Type: research

Vardenafil reduces macrophage pro-inflammatory overresponses in Cystic Fibrosis through PDE5- and CFTR-dependent mechanisms
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type li...
Source: Clinical Science - February 14, 2017 Category: Biomedical Science Authors: Noel, S., Panin, N., Beka, M., Dhooghe, B., HUAUX, F., Leal, T. Tags: PublishAheadOfPrint Source Type: research

Deletion of Hypoxia-Inducible Factor-1{alpha} in Myeloid Lineage Exaggerates Angiotensin II-Induced Formation of Abdominal Aortic Aneurysm
Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodeling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient mice. HIF-1KO and control mice were fed high-fat diet (HFD) and infused wit...
Source: Clinical Science - February 14, 2017 Category: Biomedical Science Authors: Takahara, Y., Tokunou, T., Kojima, H., Hirooka, Y., Ichiki, T. Tags: PublishAheadOfPrint Source Type: research