Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load
Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery fl...
Source: Clinical Science - August 11, 2016 Category: Biomedical Science Authors: Walsh, L. K., Restaino, R. M., Neuringer, M., Manrique, C., Padilla, J. Tags: PublishAheadOfPrint Source Type: research

Adipose-Specific Inactivation of JNK Alleviates Atherosclerosis in ApoE-deficient Mice
This study investigated whether the suppression of fat inflammation through adipose-specific JNK inactivation could protect against atherosclerosis in mice. ApoE-/- mice were crossbred with transgenic mice with adipose-specific expression of a dominant negative form of JNK (dnJNK) to generate apoE-/-/dnJNK (ADJ) mice. High-fat-high-cholesterol diet-treated ADJ mice exhibited significant attenuations of visceral fat and systemic inflammation without changes in lipid or glucose metabolism, and were protected against atherosclerosis, when compared to apoE-/- mice. Lean apoE-/- mice that received transplantation of visceral fa...
Source: Clinical Science - August 10, 2016 Category: Biomedical Science Authors: Kwok, K. H. M., Cheng, K., Hoo, R. L. C., Ye, D., Xu, A., Lam, K. S. L. Tags: PublishAheadOfPrint Source Type: research

Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208
Conclusions: Altogether, we conclude that high-volume swim training finely assures physiological cardiac remodelling by epigenetic regulation of myomiRs, because inhibition of miR-208a and 208b increases the expression of their target proteins and stimulates the interaction among metabolic, contractile and epigenetic genes. (Source: Clinical Science)
Source: Clinical Science - August 8, 2016 Category: Biomedical Science Authors: Soci, U. P. R., Fernandes, T., Barauna, V. G., Hashimoto, N. Y., Mota, G. d. F. A., Rosa, K. T., Irigoyen, M. C., Phillips, M. I., de Oliveira, E. M. Tags: PublishAheadOfPrint Source Type: research

Peroxisome proliferator-activated receptor {alpha}-dependent renoprotection of murine kidney by irbesartan
Activation of renal peroxisome proliferator-activated receptor α (PPARα) is renoprotective, but there is no safe PPARα activator for patients with chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an angiotensin II receptor blocker (ARB) widely prescribed for CKD, activates hepatic PPARα. However, Irbe's renal PPARα-activating effects and the role of PPARα signaling in the renoprotective effects of Irbe are unknown. Herein, these aspects were investigated in healthy kidneys of wild-type (WT) and Ppara -null (KO) mice and in the murine protein-overload-nephropath...
Source: Clinical Science - August 5, 2016 Category: Biomedical Science Authors: Harada, M., Kamijo, Y., Nakajima, T., Hashimoto, K., Yamada, Y., Shimojo, H., Gonzalez, F. J., Aoyama, T. Tags: PublishAheadOfPrint Source Type: research

Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men
Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men.In this randomized, double-blind cross-over trial, six overweight/obese men (BMI 25-35 kg/m2) underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive te...
Source: Clinical Science - July 27, 2016 Category: Biomedical Science Authors: van der Beek, C. M., Canfora, E. E., Lenaerts, K., Troost, F. J., Olde Damink, S. W. M., Holst, J. J., Masclee, A. A. M., Dejong, C. H. C., Blaak, E. E. Tags: PublishAheadOfPrint Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - June 6, 2016 Category: Biomedical Science Authors: Santos Almeida, A. F., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells
In this study, we showed a clinical correlation between adiponectin and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knockdown inhibited lymphangiogenesis in vitro and in vivo. We also found that adiponectin-induced VEGF-C is mediated by the CaMKII, AMPK and p38 signaling pathway. Furthermore, the expression of miR-27b was negati...
Source: Clinical Science - June 1, 2016 Category: Biomedical Science Authors: Huang, C.-Y., Chang, A.-C., Chen, H.-T., Wang, S.-W., Lo, Y.-S., Tang, C. H. Tags: PublishAheadOfPrint Source Type: research

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography
This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during...
Source: Clinical Science - June 1, 2016 Category: Biomedical Science Authors: Chowdhury, A. H., Camara, M., Martinez-Pomares, L., Zaitoun, A. M., Eremin, O., Aithal, G. P., Lobo, D. N. Tags: PublishAheadOfPrint Source Type: research

Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarisation
HNO donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure.  Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leukocyte adhesion to the endothelium and macrophage polarisation. Similar to the NO donor, glyceryl trinitrate, the HNO donors, Angeli's Salt and isopropylamine NONOate decreased leukocyte adhesion to activated human umbilical vein endothelial cells and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in the adhesion molecule ICAM-1 and ...
Source: Clinical Science - May 26, 2016 Category: Biomedical Science Authors: Andrews, K. L., Sampson, A. K., Irvine, J. C., Shihata, W. A., Michell, D., Lumsden, N. G., Lim, C., Huet, O., Kemp-Harper, B., Chin-Dusting, J. P. Tags: PublishAheadOfPrint Source Type: research

Myeloid-derived suppressor cells contribute to systemic lupus erythematosus by regulating differentiation of Th17 cells and Treg
In this study, we investigated percentage and function of MDSCs using different stages of MRL/lpr lupus mice and specimen from SLE patients with different activity. Result showed that splenic granulocytic (G)-MDSCs were significantly expanded by increasing expression chemokine receptor 1 (CCR1) in diseased MRL/lpr lupus mice and in high active SLE patients. However, percentage of monocytic (M)-MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels reactive oxygen species (ROS) through increasing gp91phox expression, and activated Toll-like receptors (TLR) 2 and absent in melanoma (AIM) 2 ...
Source: Clinical Science - May 26, 2016 Category: Biomedical Science Authors: Ji, J., Xu, J., Zhao, S., Liu, F., Qi, J., Song, Y., Ren, J., Wang, T., Dou, H., hou, y. Tags: PublishAheadOfPrint Source Type: research

Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both ERK1 pathway in HSC and hepatocyte EMT
MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of this study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in vitro and in vivo. Histological and imm...
Source: Clinical Science - May 25, 2016 Category: Biomedical Science Authors: Wu, K., Ye, C., Lin, L., Chu, Y., Ji, M., Dai, W., Zeng, X., Lin, Y. Tags: PublishAheadOfPrint Source Type: research

Effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic mice.
Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species, NADPH oxidase enzymes, and immune- inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase NOX subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE-/- mice. Plaque area analysis showed that NOX4- and NOX1-derived reactive oxygen species (ROS) c...
Source: Clinical Science - May 17, 2016 Category: Biomedical Science Authors: Di Marco, E., Gray, S. P., Chew, P., Kennedy, K., Cooper, M. E., Schmidt, H. H. H. W., Jandeleit-Dahm, K. A. Tags: PublishAheadOfPrint Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - May 3, 2016 Category: Biomedical Science Authors: Santos Almeida, A. F. J., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Tobacco Toxins Deposited on Surfaces (Third Hand Smoke) Impair Wound Healing
Third Hand Smoke (THS) is the accumulation of second hand smoke (SHS) toxins on surfaces in homes, cars, clothing and hair of smokers. It is known that 88M US nonsmokers ≥3 years old living in homes of smokers are exposed to THS toxicants and show blood cotinine levels of ≥0.05ng/ml, indicating that the toxins are circulating in their circulatory systems. The goal of this study is to investigate the mechanisms by which THS causes impaired wound healing. We show that mice living under conditions that mimic THS exposure in humans display delayed wound closure, impaired collagen deposition, altered inflammatory response...
Source: Clinical Science - April 28, 2016 Category: Biomedical Science Authors: Dhall, S., Alamat, R., Castro, A., Sarker, A. H., Mao, J.-H., Chan, A., Hang, B., Martins-Green, M. Tags: PublishAheadOfPrint Source Type: research

Modulation of Myocardial Injury and Collagen Deposition Following Ischemia/Reperfusion by Linagliptin, Liraglutide, and Both Together
In conclusion, linagliptin and liraglutide are able to improve cardiac contractile function and indices of cardiac remodeling, which may be related to their role in inhibition of ROS production and pro-inflammatory cytokines following ischemia. (Source: Clinical Science)
Source: Clinical Science - April 26, 2016 Category: Biomedical Science Authors: Wang, X., Ding, Z., Yang, F., Dai, Y., Chen, P., Theus, S., Singh, S., Budhiraja, M., Mehta, J. L. Tags: PublishAheadOfPrint Source Type: research

Macrophage TCF-4 Coactivates p65 to Potentiate Chronic Inflammation and Insulin Resistance in Mice
TCF-4 was recently identified to be a candidate gene for the cause of type 2 diabetes, with the mechanisms being not fully elucidated. Here in this study, we demonstrated that TCF-4 transgene in macrophages aggravated high fat diet-induced insulin resistance and chronic inflammation, characterized by the elevation of proinflammatory cytokines in the blood, livers and white adipose tissues as well as a proinflammatory profile of immune cells in visceral fats in mice. Mechanistically, TCF-4 functioned as a co-activator of p65 to amplify the saturated free fatty acid-stimulated promoter activity, mRNA transcription and secret...
Source: Clinical Science - April 26, 2016 Category: Biomedical Science Authors: Kang, X., hou, a., Wang, R., Liu, D., xiang, w., Xie, Q., Zhang, B., gan, l., Zheng, W., Miao, H. Tags: PublishAheadOfPrint Source Type: research

1,8-cineole potentiates IRF3-mediated antiviral response in human stem cells and an ex vivo model of rhinosinusitis
Common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial super-infections resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential of 1,8-cineole for treating primary viral infections of the respiratory tract remains unclear.In the present study, we demonstrate for the first time that 1,8-cineole potentiates Poly(I:C)-induced activity of the anti-viral transcription factor Interferon Regulatory Factor 3, while simultaneously red...
Source: Clinical Science - April 25, 2016 Category: Biomedical Science Authors: Muller, J., Greiner, J. F., Zeuner, M., Brotzmann, V., Schafermann, J., Wieters, F., Widera, D., Sudhoff, H., Kaltschmidt, B., Kaltschmidt, C. Tags: PublishAheadOfPrint Source Type: research

Colchicine Therapy in Acute Coronary Syndrome Patients acts on Caspase-1 to Suppress NLRP3 Inflammasome Monocyte Activation
Rationale
Source: Clinical Science - April 21, 2016 Category: Biomedical Science Authors: Robertson, S., Martinez, G. J., Payet, C. A., Barraclough, J. Y., Celermajer, D. S., Bursill, C., Patel, S. Tags: PublishAheadOfPrint Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - April 20, 2016 Category: Biomedical Science Authors: Almeida-Santos, A. F. J., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition versus AT1 receptor blockade alone
In conclusion, ARNI reduces proteinuria, glomerulosclerosis, and heart weight in diabetic TGR(mREN2)27 rats more strongly than ARB, and this occurs independently of BP. (Source: Clinical Science)
Source: Clinical Science - April 19, 2016 Category: Biomedical Science Authors: Roksnoer, L. C. W., van Veghel, R., Clahsen-van Groningen, M. C., de Vries, R., Garrelds, I. M., Bhaggoe, U. M., van Gool, J. M. G., Friesema, E. C. H., Leijten, F. P. J., Hoorn, E. J., Danser, A. H. J., Batenburg, W. W. Tags: PublishAheadOfPrint Source Type: research

Down-regulation of miR-192-5p protects from oxidative-stress induced-acute liver injury
Conclusions: Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury. (Source: Clinical Science)
Source: Clinical Science - April 18, 2016 Category: Biomedical Science Authors: Roy, S., Benz, F., Alder, J., Bantel, H., Janssen, J., Vucur, M., Gautheron, J., Schneider, A. T., Schueller, F., Loosen, S., Luedde, M., Koch, A., Tacke, F., Luedde, T., Trautwein, C., Roderburg, C. Tags: PublishAheadOfPrint Source Type: research

Dysregulation of ossification related microRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis
This study aimed to determine whether expression of ossification related microRNAs is related to differentiation intro circulating osteogenic progenitor cells (COPCs) in patients with CAVD.This study included 46 patients with AS and 46 controls. Twenty nine patients underwent surgical aortic valve replacement (AVR) and 17 underwent transcatheter aortic valve implantation (TAVI).The number of COPCs was higher in the AS group than in the controls (P
Source: Clinical Science - April 14, 2016 Category: Biomedical Science Authors: Takahashi, K., Satoh, M., Takahashi, Y., Osaki, T., Nasu, T., Tamada, M., Okabayashi, H., Nakamura, M., Morino, Y. Tags: PublishAheadOfPrint Source Type: research

Therapeutic inhibition of phospholipase D1 suppresses hepatocellular carcinoma
Hepatocellular carcinoma (HCC) represents a leading cause of deaths worldwide. Novel therapeutic targets for HCC are needed. Phospholipase D (PLD) is involved in cell proliferation and migration, however, its role in HCC remains unclear. Here we show that PLD1, but not PLD2, was overexpressed in HCC cell lines (HepG2, Bel-7402, and Bel-7404) compared to the normal human L-02 hepatocytes. PLD1 was required for the proliferation, migration, and invasion of HCC cells without affecting apoptosis and necrosis and PLD1 overexpression was sufficient to promote those effects. By using HCC xenograft models, we demonstrated that the...
Source: Clinical Science - April 13, 2016 Category: Biomedical Science Authors: Xiao, J., Sun, Q., Bei, Y., Zhang, L., Dimitrova-Shumkovska, J., Lv, D., Yang, Y., Cao, Y., Zhao, Y., Song, M., Song, Y., Wang, F., Yang, C. Tags: PublishAheadOfPrint Source Type: research

Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis
Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumor cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT rates of appearance were measured by stable isotope methodology before and after ...
Source: Clinical Science - April 7, 2016 Category: Biomedical Science Authors: Engelen, M. P., Safar, A. M., Bartter, T., Koeman, F., Deutz, N. E. Tags: PublishAheadOfPrint Source Type: research

Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction
In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leukocytes, thereby promoting post-infarct inflammation. (Source: Clinical Science)
Source: Clinical Science - April 5, 2016 Category: Biomedical Science Authors: Gao, X.-M., Moore, X.-L., Liu, Y., Wang, X.-Y., Han, L.-P., Su, Y., Tsai, A., Xu, Q., Zhang, M., Lambert, G. W., Kiriazis, H., Gao, W., Dart, A. M., Du, X.-J. Tags: PublishAheadOfPrint Source Type: research

Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men
Aims/hypothesis Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue depots of metabolically distinct humans are scarce.Methods Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c
Source: Clinical Science - April 4, 2016 Category: Biomedical Science Authors: Verboven, K., Hansen, D., Moro, C., Eijnde, B. O., Hoebers, N., Knol, J., Bouckaert, W., Dams, A., Blaak, E. E., Jocken, J. W. Tags: PublishAheadOfPrint Source Type: research

Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: Role of MIR-143
A predisposing factor for development of the hyperglycemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is upregulated via changes in miR-143 expression in the placenta of women with GDM. Placental tissue was collected at term from women with A1GDM (c...
Source: Clinical Science - March 31, 2016 Category: Biomedical Science Authors: Muralimanoharan, S., Maloyan, A., Myatt, L. Tags: PublishAheadOfPrint Source Type: research

Hypertensive Retinopathy in a Transgenic Angiotensin-based Model
Severe hypertension destroys eyesight. The renin-angiotensin system may contribute. We relied on an established angiotensin, Ang II-elevated double-transgenic model (dTGR) and same-background Sprague-Dawley rat (SD) controls. In dTGR plasma levels of Ang II were increased. We determined the general retinal phenotype and observed degeneration of ganglion cells that we defined as vascular degeneration. We also inspected relevant gene expressions and lastly observed alterations in the outer blood-retinal barrier. We found that both scotopic a-wave and b-wave as well as oscillatory potential amplitude were significantly decrea...
Source: Clinical Science - March 29, 2016 Category: Biomedical Science Authors: Reichhart, N., Haase, N., Crespo-Garcia, S., Skosyrski, S., Herrspiegel, C., Kociok, N., Fuchshofer, R., Dillinger, A., Poglitsch, M., Muller, D. N., Joussen, A. M., Luft, F. C., Dechend, R., Strauss, O. Tags: PublishAheadOfPrint Source Type: research

A potent Nrf2 activator, dh404, bolsters antioxidant capacity in glial cells and attenuates ischaemic retinopathy
In conclusion, agents such as dh404 that reduce oxidative stress and promote antioxidant capacity offer a novel approach to lessen the vascular and glial cell damage that occurs in ischemic retinopathies. (Source: Clinical Science)
Source: Clinical Science - March 22, 2016 Category: Biomedical Science Authors: Deliyanti, D., Lee, J. Y., Petratos, S., Meyer, C., Ward, K., Wilkinson-Berka, J. L., de Haan, J. B. Tags: PublishAheadOfPrint Source Type: research

miR-92b promotes tumor proliferation, migration, and invasion by targeting RECK in osteosarcoma
In this study, we focused on the expression, function, and mechanisms of miR-92b in osteosarcoma development. miR-92b was upregulated in osteosarcoma cell lines and tissues.miR-92b upregulation was correlated with poor prognosis in osteosarcoma. Overexpression ofmiR-92b promoted osteosarcoma cell proliferation,migration, and invasion, which was abrogated by miR-92b inhibition.Reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was identified as the direct and functional target of miR-92b in osteosarcoma. Importantly, restoring RECK expression abrogated increases in cell growth, motility, and invasiveness indu...
Source: Clinical Science - March 18, 2016 Category: Biomedical Science Authors: Zhou, Z., Wang, Z., Wei, H., Wu, S., Wang, X., Xiao, J. Tags: PublishAheadOfPrint Source Type: research

Mitochondrial function and glucose metabolism in the placenta with 2 gestational diabetes mellitus: Role of MIR-143
A predisposing factor for development of the hyperglycemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is upregulated via changes in miR-143 expression in the placenta of women with GDM. Placental tissue was collected at term from women with A1GDM (c...
Source: Clinical Science - March 18, 2016 Category: Biomedical Science Authors: Muralimanoharan, S., Maloyan, A., Myatt, L. Tags: PublishAheadOfPrint Source Type: research

Paraoxonase-1 overexpression prevents experimental abdominal aortic aneurysm progression
In conclusion, decreased circulating PON1 activity is associated to human and experimental AAA. PON1 overexpression in mice protects against AAA progression by reducing oxidative stress, apoptosis and inflammation, suggesting that strategies aimed at increasing PON1 activity could prevent AAA. (Source: Clinical Science)
Source: Clinical Science - March 18, 2016 Category: Biomedical Science Authors: BURILLO, E., TARIN, C., TORRES-FONSECA, M. M., FERNANDEZ-GARCIA, C. E., MARTINEZ-PINNA, R., MARTINEZ-LOPEZ, D., LLAMAS-GRANDA, P., CAMAFEITA, E., LOPEZ, J. A., VEGA DE CENIGA, M., AVIRAM, M., EGIDO, J., BLANCO-COLIO, L. M., MARTIN-VENTURA, J. L. Tags: PublishAheadOfPrint Source Type: research

Impaired glucose tolerance after brief heat exposure: a randomized crossover study in healthy young men
The objective of this project was to examine the isolated and combined effects of experimental short-term mild heat exposure and metabolic level on glycoregulation. Two experimental randomized crossover studies were conducted. Ten healthy young men participated in study A, which comprised four sessions in a fasting state at two metabolic levels (rest and exercise at 60% of maximal oxygen uptake for 40 minutes) in two environmental temperatures (warm: 31°C and control: 22°C). Each session ended with an ad libitum meal, resulting in similar energy intake across sessions. In study B, twelve healthy young men underwent...
Source: Clinical Science - March 15, 2016 Category: Biomedical Science Authors: Faure, C., Charlot, K., Henri, S., Hardy-dessources, M.-d., Hue, O., Antoine-Jonville, S. Tags: PublishAheadOfPrint Source Type: research

IL-10-producing regulatory B cells suppressed effector T but enhanced regulatory T cells in chronic HBV infection
Conclusions: Elevated Bregs can suppress effector T but enhance Treg functions, which might influence immune tolerance in chronic HBV infection. (Source: Clinical Science)
Source: Clinical Science - March 15, 2016 Category: Biomedical Science Authors: Liu, Y., Cheng, L.-s., Wu, S.-d., Wang, S.-q., Li, L., She, W.-m., Li, J., Wang, J.-y., Jiang, W. Tags: PublishAheadOfPrint Source Type: research

Endothelial dysfunction in DOCA-salt hypertensive mice: Role of neuronal nitric oxide synthase-derived hydrogen peroxide
Endothelial dysfunction is a common problem associated with hypertension and is considered a precursor to the development of micro- and macrovascular complications. The present study investigated the involvement of neuronal nitric oxide synthase (nNOS) and hydrogen peroxide (H2O2) in the impaired endothelium-dependent vasodilation of the mesenteric arteries of DOCA-salt hypertensive mice (DOCA-salt). Myograph studies were used to investigate the endothelium-dependent vasodilator effect of acetylcholine (ACh). The expression and phosphorylation of nNOS and endothelial NOS (eNOS) were studied by western blot analysis. Immuno...
Source: Clinical Science - March 14, 2016 Category: Biomedical Science Authors: Silva, G. C., Silva, J. F., Diniz, T. F., Lemos, V. S., Cortes, S. F. Tags: PublishAheadOfPrint Source Type: research

Ptp1b deletion in pro-opiomelanocortin neurons increases energy expenditure and impairs endothelial function via TNF-{alpha} dependent mechanisms
Conclusion: POMC-Ptp1b deletion increases plasma TNF-α levels, which contribute to body weight regulation via increased energy expenditure and impair endothelial function via COX-2 and ROS-dependent mechanisms. (Source: Clinical Science)
Source: Clinical Science - March 2, 2016 Category: Biomedical Science Authors: Bruder-Nascimento, T., Kennard, S., Antonova, G., Mintz, J. D., Bence, K. K., Belin de Chantemele, E. J. Tags: PublishAheadOfPrint Source Type: research

High fat diet increases O-GlcNAc levels in cerebral arteries: a link to vascular dysfunction associated with hyperlipidemia/obesity?
Obesity and high fat intake induce alterations in vascular function and structure. Aberrant O -GlcNAcylation ( O -GlcNAc) of vascular proteins has been implicated in vascular dysfunction associated with cardiovascular and metabolic diseases. In the present study, we tested the hypothesis that high-fat diet (HFD)-mediated increases in O -GlcNAc-modified proteins contribute to cerebrovascular dysfunction. O -GlcNAc-protein content was increased in arteries from male Wistar rats treated with a HFD (45% fat) for 12 weeks vs. arteries from rats on control diet (CD). HFD augmented body weight [(g) 550±10 vs. 502±10...
Source: Clinical Science - February 29, 2016 Category: Biomedical Science Authors: Lima, V. V., Giachini, F. F., Matsumoto, T., Li, W., Bressan, A. F. M., Chawla, D., Webb, R. C., Ergul, A., Tostes, R. C. Tags: PublishAheadOfPrint Source Type: research

Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphedema model
In conclusion, the attempts to locally block EMILIN1 degradation represent the basis for a novel "ECM" pharmacological approach to assess new lymphedema treatments. (Source: Clinical Science)
Source: Clinical Science - February 26, 2016 Category: Biomedical Science Authors: Pivetta, E., Wassermann, B., Del Bel Belluz, L., Danussi, C., Modica, T. M., Maiorani, O., Bosisio, G., Boccardo, F., Canzonieri, V., Colombatti, A., Spessotto, P. Tags: Translational Science Source Type: research

Mapping Time-course Mitochondrial Adaptations in the Kidney in Experimental Diabetes
Oxidative phosphorylation drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homeostasis. In diabetic kidney disease, mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics, have not been previously documented. Here, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological c...
Source: Clinical Science - February 17, 2016 Category: Biomedical Science Authors: Coughlan, M. T., Nguyen, T.-v., Penfold, S. A., Higgins, G. C., Thallas-Bonke, V., Tan, S. M., Van Bergen, N. J., Sourris, K. C., Harcourt, B. E., Thorburn, D. R., Trounce, I. A., Cooper, M. E., Forbes, J. M. Tags: PublishAheadOfPrint Source Type: research

Tripartite Motif 32 Prevents Pathological Cardiac Hypertrophy
In conclusion, our study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodeling by blocking Akt-dependent signaling. Therefore, TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. (Source: Clinical Science)
Source: Clinical Science - February 16, 2016 Category: Biomedical Science Authors: Chen, L., Huang, J., Ji, Y., Zhang, X., Wang, P., Deng, K., Jiang, X., Ma, G., Li, H. Tags: PublishAheadOfPrint Source Type: research

Emulsified Isoflurane Postconditioning Cardioprotection is Lost in Rats with Streptozotocin-induced Diabetes Due to The Impairment of Brg1/Nrf2/STAT3 Signaling
In conclusion, IsoPostC confers cardioprotection through Brg1/Nrf2/STAT3 signaling, and impairment of this pathway may be responsible for the loss of IsoPostC cardioprotection in diabetes. (Source: Clinical Science)
Source: Clinical Science - February 4, 2016 Category: Biomedical Science Authors: Wang, Y., Li, H., Huang, H., Liu, S., mao, X., Wang, S., Wong, S. S.-c., Xia, Z., Irwin, M. G. Tags: PublishAheadOfPrint Source Type: research

Aberrantly Methylated DNA Regions Lead to Low Activation of CD4+ T Cells in IgA Nephropathy
In conclusion, we identified for the first time some specific DNA regions abnormally methylated in IgAN patients that led to the reduced TCR signal strength of the CD4+ T cells and to their anomalous response and activation that could explain the T helper cell imbalance. This study reveals new molecular mechanisms underlying the abnormal CD4+ T cell response in IgAN patients. (Source: Clinical Science)
Source: Clinical Science - February 4, 2016 Category: Biomedical Science Authors: Sallustio, F., Serino, G., Cox, S. N., Dalla Gassa, A., Curci, C., De Palma, G., Banelli, B., Zaza, G., Romani, M., Schena, F. P. Tags: PublishAheadOfPrint Source Type: research

Latrunculin B Modulates Electrophysiological Characteristics and Arrhythmogenesis in Pulmonary Veins Cardiomyocytes
In conclusion, Lat-B regulates PV electrophysiological characteristics and attenuates stretch-induced arrhythmogenesis. (Source: Clinical Science)
Source: Clinical Science - February 2, 2016 Category: Biomedical Science Authors: Lu, Y.-y., Lin, Y. K., Wen, Z.-h., Chen, Y.-C., Chen, S.-A., Chen, Y.-J. Tags: PublishAheadOfPrint Source Type: research

Intranasal vaccination with gamma-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B cells and innate IL-17 responses.
Generating a pneumococcal vaccine that is serotype-independent and cost effective remains a global challenge. Gamma-irradiation has been used widely to sterilize biological products. It can also be utilised as an inactivation technique to generate whole cell bacterial and viral vaccines with minimal impact on pathogen structure and antigenic determinants. In the present study, we utilised gamma-irradiation to inactivate an unencapsulated Streptococcus pneumoniae strain Rx1 with an unmarked deletion of the autolysin gene lytA and with the pneumolysin gene ply replaced with an allele encoding a non-toxic pneumolysoid (PdT) (...
Source: Clinical Science - February 1, 2016 Category: Biomedical Science Authors: Babb, R., Chen, A., Hirst, T. R., Kara, E. E., McColl, S. R., Ogunniyi, A. D., Paton, J. C., Alsharifi, M. Tags: PublishAheadOfPrint Source Type: research

Mapping Time-course Mitochondrial Adaptations in the Kidney in Experimental Diabetes
Oxidative phosphorylation drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homeostasis. In diabetic kidney disease, mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics, have not been previously documented. Here, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological c...
Source: Clinical Science - February 1, 2016 Category: Biomedical Science Authors: Coughlan, M. T., Nguyen, T.-v., Penfold, S. A., Higgins, G. C., Thallas-Bonke, V., Tan, S. M., Van Bergen, N. J., Sourris, K. C., Harcourt, B. E., Thorburn, D. R., Trounce, I. A., Cooper, M. E., Forbes, J. M. Tags: PublishAheadOfPrint Source Type: research

Interleukin-1{beta} induces fibroblast growth factor 2 expression and subsequently promotes endothelial progenitor cell angiogenesis in chondrocytes
Arthritis is a process of chronic inflammation that results in joint damage. Interleukin-1β (IL-1β) is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1β in the angiogenesis of chondrocytes remains unknown. Here, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1β increased the expression of fibroblast growth factor (FGF)-2, a potent angiogenic inducer, and then promoted endothelial progenitor cell (EPC) tube formation an...
Source: Clinical Science - January 29, 2016 Category: Biomedical Science Authors: Chien, S.-y., Huang, C.-y., Tsai, C.-h., Wang, S.-w., Lin, Y.-M., Tang, C. H. Tags: PublishAheadOfPrint Source Type: research

EEF1D modulates proliferation and epithelial-to-mesenchymal transition in oral squamous cell carcinoma
Eukaryotic translation elongation factor 1 delta (EEF1D) is a subunit of the elongation factor 1 complex of proteins that mediates the elongation process during protein synthesis via enzymatic delivery of aminoacyl tRNAs to the ribosome. While the functions of EEF1D in the translation process are recognized, EEF1D expression was found to be unbalanced in tumors. Here we demonstrated the overexpression of EEF1D in oral squamous cell carcinoma (OSCC), and revealed that EEF1D and protein interaction partners promote the activation of cyclin D1 and vimentin proteins. EEF1D knockdown in OSCC reduced cell proliferation and induc...
Source: Clinical Science - January 28, 2016 Category: Biomedical Science Authors: Flores, I. L., Kawahara, R., Miguel, M. C. C., Granato, D. C., Domingues, R. R., MacEdo, C. C. S., Carnielli, C. M., Yokoo, S., Rodrigues, P. C., Monteiro, B. V. B., Oliveira, C. E., Salmon, C. R., Nociti, F. H., Lopes, M. A., Santos-silva, A., Winck, F. Tags: PublishAheadOfPrint Source Type: research

NADPH oxidase 2 plays a role in experimental corneal neovascularisation
In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularisation and inflammation in humans. (Source: Clinical Science)
Source: Clinical Science - January 26, 2016 Category: Biomedical Science Authors: Chan, E. C., Van Wijngaarden, P., Chan, E., Ngo, D., Wang, J.-h., Peshavariya, H. M., Dusting, G. J., Liu, G.-S. Tags: PublishAheadOfPrint Source Type: research

Oral Estrogen Reverses Ovariectomy-Induced Morning Surge Hypertension in Growth Restricted Mice
Perinatal growth restriction is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal growth restriction (GR) programs hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy estrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the 10th percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-ovariectomy (OVX), and post-OVX with oral estrogen replacemen...
Source: Clinical Science - January 21, 2016 Category: Biomedical Science Authors: Haskell, S. E., Peotta, V., Reinking, B. E., Zhang, C., Zhu, V., Kenkel, E. J., Roghair, R. D. Tags: PublishAheadOfPrint Source Type: research

Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of type 1 diabetic mice
Fenofibrate (FF), as a peroxisome proliferator-activated receptor-α agonist, has been used clinically for decades tolower lipid levels. Here we examined whether FF can be repurposed to prevent the pathogenies of the heart in type 1 diabetes and to describe the underlying mechanism of its action. Streptozotocin-induced diabetic mice and their age-matched control mice were treated with vehicle or FF by gavage every other day for 3 or 6 months. FF prevented diabetes-induced cardiac dysfunction (e.g. decreased ejection fraction and hypertrophy), inflammation, and remodeling. FF also increased cardiac expression of fibrob...
Source: Clinical Science - January 21, 2016 Category: Biomedical Science Authors: Zhang, J., Cheng, Y., Gu, J., Wang, S., Zhou, S., Wang, Y., Tan, Y., Feng, W., Fu, Y., Mellen, N., Cheng, R., Ma, J., Zhang, C., Li, Z., Cai, L. Tags: PublishAheadOfPrint Source Type: research