Hypertrophied myocardium is vulnerable to ischemia reperfusion injury and refractory to rapamycin-induced protection due to increased oxidative/nitrative stress
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. Rapamycin produced marked cardiopro...
Source: Clinical Science - November 24, 2017 Category: Biomedical Science Authors: Ma, L.-L., Yin, P.-P., Li, Y., Kong, F.-J., Guo, J.-J., Shi, H.-T., Zhu, J.-B., Zou, Y.-Z., Ge, J.-B. Tags: PublishAheadOfPrint Source Type: research

TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet-fed mouse
Conclusion/interpretation: This study shows for the first time that TRAIL is effective when administered after disease onset. In addition, our data sheds light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD. (Source: Clinical Science)
Source: Clinical Science - November 22, 2017 Category: Biomedical Science Authors: Bernardi, S., Toffoli, B., Tisato, V., Bossi, F., Biffi, S., Lorenzon, A., Zauli, G., Secchiero, P., Fabris, B. Tags: PublishAheadOfPrint Source Type: research

Rodent Vertical Sleeve Gastrectomy Alters Maternal Immune Health and Feto-placental Development
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 abnorma...
Source: Clinical Science - November 22, 2017 Category: Biomedical Science Authors: Spann, R. A., Lawson, W. J., Bidwell, G. L., Zamarripa, C. A., Maranon, R. O., Bandyopadhyay, S., Taylor, E. R., Reckelhoff, J. F., Garrett, M. R., Grayson, B. E. Tags: PublishAheadOfPrint Source Type: research

Does sympathetic dysfunction occur before denervation in pure autonomic failure?
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. Methods: The abund...
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Guo, L., Esler, M. D., Sari, C., Phillips, S., Lambert, E. A., Straznicky, N. E., Lambert, G. W., Corcoran, S. J. Tags: PublishAheadOfPrint Source Type: research

Vascular Dysfunction in the Stroke Prone Spontaneously Hypertensive Rat Is Dependent on Constrictor Prostanoid Activity and Y Chromosome Lineage
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. Measurement of prostacyclin, the most abundant product of COX in the vascula...
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Khan, S. I., Andrews, K. L., Jefferis, A.-M., Jennings, G. L., Sampson, A. K., Chin-Dusting, J. P. F. Tags: PublishAheadOfPrint Source Type: research

Therapeutic Effect of a Novel Wnt Pathway Inhibitor on Cardiac Regeneration after Myocardial Infarction
In conclusion, porcupine inhibitor CGX1321 reduces MI injury by limiting fibrosis and promoting regeneration. It promotes cardiomyocyte proliferation by stimulating cell cycle regulating genes with a Hippo/YAP independent pathway. (Source: Clinical Science)
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Zeng, C., Yang, D., Fu, W., Li, L., Xia, X., Liao, Q., Yue, R., Chen, H., Chen, X., An, S., Wang, W. E. Tags: PublishAheadOfPrint Source Type: research

Hepatic accumulation of S-Adenosylmethionine in hamsters with non-alcoholic-fatty liver disease associated to metabolic syndrome under selenium and vitamin E deficiency.
In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation. (Source: Clinical Science)
Source: Clinical Science - November 9, 2017 Category: Biomedical Science Authors: del Bas, J. M., Rodriguez, B., Puiggros, F., Marine, S., Rodriguez, M. A., Morina, D., Armengol, L., Caimari, A., Arola, L. Tags: PublishAheadOfPrint Source Type: research

The shifted balance between circulating follicular regulatory T cells and follicular helper T cells in patients with ulcerative colitis
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). Disease activity was evaluated by the Mayo clinic score. Compared to controls, UC patients exhibited...
Source: Clinical Science - November 6, 2017 Category: Biomedical Science Authors: Wang, X., Zhu, Y., Zhang, M., Hou, J., Wang, H., Jiang, Y., Wang, H., Gao, P. Tags: PublishAheadOfPrint Source Type: research

Mesenchymal stromal cells improve human islet function through released products and extracellular matrix
Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM. (Source: Clinical Science)
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Arzouni, A. A., Vargas-Seymour, A., Rackham, C. L., Dhadda, P., Huang, G.-C., Choudhary, P., Nardi, N., King, A. J. F., Jones, P. M. Tags: PublishAheadOfPrint Source Type: research

Relaxin contributes to the regulation of arterial pressure in adult female mice
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. Mean arterial pressure (MAP) was measured via radiotelemetry ...
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Mirabito Colafella, K. M., Samuel, C. S., Denton, K. M. Tags: PublishAheadOfPrint Source Type: research

Loss of microRNA-22 prevents high fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy
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. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alt...
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Diniz, G. P., Huang, Z.-P., Liu, J., Chen, J., Ding, J., Fonseca, R. I., Barreto-Chaves, M. L., Donato, J., Hu, X., Wang, D.-Z. Tags: PublishAheadOfPrint Source Type: research

Autoantibodies against AT1 and {alpha}1-Adrenergic Receptors Predict Arterial Stiffness Progression in Normotensive Subjects Over a 5-Year Period
Objective: Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT1 receptor (AT1-AAs) and α1-Adrenergic receptor (α1-AAs) are important in the pathogenesis of hypertension. We identified the types of AT1-AAs and α1-AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Methods: Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types o...
Source: Clinical Science - November 2, 2017 Category: Biomedical Science Authors: Li, G., Cao, Z., Wu, X.-w., Wu, H.-k., Ma, Y., Wu, B., Wang, W.-q., Cheng, J., Zhou, Z.-h., Tu, Y.-c. Tags: PublishAheadOfPrint Source Type: research

GLP-1 response to sequential mixed meals: influence of insulin resistance.
Previous work has shown that potentiation of insulin release is impaired in non-diabetic insulin resistance; we tested the hypothesis that this defect may be related to altered GLP-1 release. On consecutive days, 82 non-diabetic individuals, classified as insulin sensitive (IS, n=41) or insulin resistant (IR, n=41) by euglycaemic clamp, were given two sequential mixed meals with standard (75 g, LCD) or double (150 g, HCD) carbohydrate content. Plasma glucose, insulin, C-peptide, NEFA and GLP-1 concentrations were measured; β-cell function (glucose sensitivity and potentiation) was resolved by mathematical modelling. F...
Source: Clinical Science - November 2, 2017 Category: Biomedical Science Authors: Rebelos, E., Astiarraga, B., Bizzotto, R., Mari, A., Manca, M. L., Gonzalez, A., Mendez, A., Martinez, C. A., Hurwitz, B. E., Ferrannini, E. Tags: PublishAheadOfPrint Source Type: research

Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.
This study investigated the interplay of these factors on junctional occupancy of VE-cadherin and macromolecular leakage in human endothelial monolayers and the perfused placental microvascular bed.  Whilst VEGF-A165a (50 ng/ml) increased endothelial monolayer albumin permeability (p0.05) or PlGF (p>0.05) did not. Moreover, VEGF-A165b (100 ng/ml; p0.05) inhibited VEGF-A165a-induced permeability when added singly. PlGF abolished the VEGF-A165b-induced reduction of VEGF-A165a mediated permeability (p>0.05); PlGF was found to compete with VEGF-A165b for binding to Flt-1 at equimolar affinity. Junctional occupancy o...
Source: Clinical Science - October 20, 2017 Category: Biomedical Science Authors: Pang, V., Bates, D. O., Leach, L. Tags: PublishAheadOfPrint Source Type: research

Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged
Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤ 35 years) and 19 aged (≥ 60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound an...
Source: Clinical Science - October 20, 2017 Category: Biomedical Science Authors: Marley, C. J., Hodson, D., Brugniaux, J. V., Fall, L., Bailey, D. M. Tags: PublishAheadOfPrint Source Type: research

Natural Killer Cells Mediate Pathophysiology in Response to Reduced Uterine Perfusion Pressure
Preeclampsia is associated with hypertension, small-for-gestational-age babies and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia. RUPP was induced on gestation day (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti-asi...
Source: Clinical Science - October 17, 2017 Category: Biomedical Science Authors: Elfarra, J., Amaral, L. M., McCalmon, M., Scott, J. D., Cunningham, M. W., Gnam, A., Ibrahim, T., LaMarca, B., Cornelius, D. C. Tags: PublishAheadOfPrint Source Type: research

Alterations in Endothelin Type B Receptor Contribute to Microvascular Dysfunction in Women Who Have Had Preeclampsia
Microvascular dysfunction originating during a preeclamptic pregnancy persists postpartum and likely contributes to increased CVD risk in these women. One putative mechanism contributing to this dysfunction is increased vasoconstrictor sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type-B (ETBR). We evaluated ET-1 sensitivity, ETAR and ETBR contributions to ET-1-mediated constriction, and the mechanistic role of  ETBR in endothelium-dependent dilation in vivo in the microvasculature of postpartum women who had preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=...
Source: Clinical Science - October 17, 2017 Category: Biomedical Science Authors: Stanhewicz, A. E., Jandu, S., Santhanam, L., Alexander, L. M. Tags: PublishAheadOfPrint Source Type: research

The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial basement membranes of arteries. This project tested the hypotheses that pial-glial basement membranes of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2 year old dog, whereas the post-mortem electron microscopy wa...
Source: Clinical Science - October 11, 2017 Category: Biomedical Science Authors: Dobson, H., MacGregor Sharp, M., Cumpsty, R., Criswell, T. P., Wellman, T., Finucane, C., Sullivan, J. M., Weller, R. O., Verma, A., Carare, R. O. Tags: PublishAheadOfPrint Source Type: research

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decrease elastase-induced AAA development.
In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. (Source: Clinical Science)
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Fernandez-Garcia, C.-E., Tarin, C., Roldan-Montero, R., Martinez-Lopez, D., Torres-Fonseca, M., Lindhot, J. S., Vega de Ceniga, M., Egido, J., Lopez de Andres, N., Blanco-Colio, L.-M., Martin-Ventura, J.-L. Tags: PublishAheadOfPrint Source Type: research

The structure of the perivascular compartment in the old canine brain: a case study
Dilatation of periarteriolar spaces in MRI of the ageing human brains occurs in white matter, basal ganglia and midbrain but not in cerebral cortex. Perivenous collagenous occurs in periventricular but not in subcortical white matter. Here we test the hypotheses that (a) the capacity for dilatation of periarteriolar spaces correlates with the anatomical distribution of leptomeningeal cells coating intracerebral arteries; (b) the regional development of perivenous collagenous in the white matter correlates with the population of intramural cells in the walls of veins. The anatomical distribution of leptomeningeal and intram...
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Criswell, T. P., MacGregor Sharp, M., Dobson, H., Finucane, C., Weller, R. O., Verma, A., Carare, R. O. Tags: PublishAheadOfPrint Source Type: research

Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men
Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS and muscle energy metabolism in older men. During 13C6-phenylalanine infusion 16 men (~70y) consumed 15g EAA with (n=8, FED+LEU ) or wi...
Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Mitchell, W. K., Phillips, B. E., Hill, I., Greenhaff, P., Lund, J. N., Williams, J. P., Rankin, D., Wilkinson, D. J., Smith, K., Atherton, P. J. Tags: PublishAheadOfPrint Source Type: research

Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease
Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel wallsthat participates in the maintenance of vascular homeostasis, can be downregulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an electi...
Source: Clinical Science - September 28, 2017 Category: Biomedical Science Authors: Martin-Nunez, E., Lopez-Castillo, A., Delgado-Molinos, A., Ferri, C., Rodriguez-Ramos, S., Cerro, P., Perez-Delgado, N., Castro, V., Hernandez-Carballo, C., Mora-Fernandez, C., Donate-Correa, J., Navarro-Gonzalez, J. F. Tags: PublishAheadOfPrint Source Type: research

DLX3 promotes bone marrow mesenchymal stem cells proliferation through H19/miR-675 axis
The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis. We found that BMSCs derived from the TDO patient (TDO-BMSCs) had stronger proliferation abilit...
Source: Clinical Science - September 28, 2017 Category: Biomedical Science Authors: Zhao, N., Zeng, L., Liu, Y., Han, D., Liu, H., Xu, J., Jiang, Y., Li, C., Cai, T., Feng, H., Wang, Y. Tags: PublishAheadOfPrint Source Type: research

Cannabidiol and Palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
Conclusion: PEA and CBD are anti-inflammatory in the human colon.  This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy. (Source: Clinical Science)
Source: Clinical Science - September 27, 2017 Category: Biomedical Science Authors: Couch, D. G., Tasker, C., Theophilidou, E., Lund, J. N., O'Sullivan, S. E. Tags: PublishAheadOfPrint Source Type: research

Intake of chocolate liquor increases vascular lesions in apoE-knockout mice
Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared to the control group, mice fed the chocola...
Source: Clinical Science - September 25, 2017 Category: Biomedical Science Authors: Yazdekhasti, N., Brandsch, C., Hirche, F., Kuhn, J., Schloesser, A., Esatbeyoglu, T., Huebbe, P., Wolffram, S., Rimbach, G., Stangl, G. I. Tags: PublishAheadOfPrint Source Type: research

Sulfur dioxide suppresses inflammatory response by sulfenylating NF-{kappa}B p65 at cysteine 38 in a rat model of acute lung injury
This study was designed to investigate whether endogenous sulfur dioxide (SO2) controlled pulmonary inflammation in a rat model of oleic acid (OA)-induced acute lung injury (ALI). In this model, adenovirus expressing aspartate aminotransferase (AAT) 1 was delivered to the lungs, and the levels of SO2 and pro-inflammatory cytokines in rat lung tissues were measured. In the human alveolar epithelial cell line A549, the nuclear translocation and DNA binding activities of wild-type (wt) and C38S NF-B p65 were detected. GFP-tagged C38S p65 was purified from HEK 293 cells, and the sulfenylation of NF-B p65 was studied. OA caused...
Source: Clinical Science - September 21, 2017 Category: Biomedical Science Authors: Chen, S., Huang, Y., Liu, Z., Yu, W., Zhang, H., Li, K., Yu, X., Tang, C., Zhao, B., Du, J., Jin, H. Tags: PublishAheadOfPrint Source Type: research

Intake of chocolate liquor increases vascular lesions in apoE-knockout mice
Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared to the control group, mice fed the chocola...
Source: Clinical Science - September 21, 2017 Category: Biomedical Science Authors: Yazdekhasti, N., Brandsch, C., Hirche, F., Kuhn, J., Schloesser, A., Esatbeygolu, T., Huebbe, P., Wolffram, S., Rimbach, G., Stangl, G. I. Tags: PublishAheadOfPrint Source Type: research

Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets
Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat 'controls' (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men wi...
Source: Clinical Science - September 18, 2017 Category: Biomedical Science Authors: Umpleby, A. M., Shojaee-Moradie, F., Fielding, B., Li, X., Marino, A., Alsini, N., Isherwood, C., Jackson, N., Ahmad, A., Stolinski, M., Lovegrove, J. A., Johnsen, S., Mendis, J., Wright, J., Wilinska, M. E., Hovorka, R., Bell, J., Thomas, L. E., Frost, G Tags: PublishAheadOfPrint Source Type: research

Pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) protects against atherosclerotic plaque formation in the LDLR-/- mouse model of atherosclerosis.
Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in LDLR-/- mouse model of atherosclerosis. Acute (single dose) or chronic PTP1B inhibitor (trodusquemine) treatment of LDLR-/- mice decreased weight gain...
Source: Clinical Science - September 12, 2017 Category: Biomedical Science Authors: Thompson, D., Morrice, N., Grant, L., Le Sommer, S., Lees, E. K., Mody, N., Wilson, H. M., Delibegovic, M. Tags: PublishAheadOfPrint Source Type: research

Genetic diagnosis of polycystic kidney disease, Alport syndrome and thalassemia minor in a large Chinese family
Conclusion : A novel pathogenic PKD1 mutation (c.3903delC) and a (--SEA) thalassemia deletion were found to be responsible for the clinical symptoms in this family. The reported pathogenic COL4a5 variant (c.2858G>T, rs78972735) wasn't pathogenic alone. (Source: Clinical Science)
Source: Clinical Science - September 1, 2017 Category: Biomedical Science Authors: Miao, Y., Xiong, J., Zhang, X., Huang, H., Yu, L., Chen, J., Deng, W., Xu, H., Liu, R., Xiang, C., Xu, X., Xiong, F. Tags: PublishAheadOfPrint Source Type: research

Overexpression of TrpC5 promotes tumor metastasis via the HIF-1{alpha}/Twist signaling pathway in colon cancer
In cancer cells, the intracellular Ca2+ ([Ca2+]i) homeostasis is altered, and this is involved in tumor initiation, progression, and metastasis. However, little is known about the underlying mechanisms. Here, we report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca2+ channel, is correlated with tumor metastasis in colon cancer patients. Moreover, in colon cancer cells, overexpression TrpC5 caused a robust [Ca2+]i rise, decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation. Interestingly, we found that TrpC5...
Source: Clinical Science - September 1, 2017 Category: Biomedical Science Authors: Chen, Z., Zhu, Y., Dong, Y., Zhang, P., Han, X., Jin, J., Ma, X. Tags: PublishAheadOfPrint Source Type: research

Genetic diagnosis of polycystic kidney disease, Alport syndrome and thalassemia minor in a large Chinese family
Conclusion : A novel pathogenic PKD1 mutation (c.3903delC) and a (--SEA) thalassemia deletion were found to be responsible for the clinical symptoms in this family. The reported pathogenic COL4a5 variant (c.2858G>T, rs78972735) wasn't pathogenic alone. (Source: Clinical Science)
Source: Clinical Science - August 21, 2017 Category: Biomedical Science Authors: Miao, Y., Xiong, J., Zhang, X., Huang, H., Yu, L., Chen, J., Deng, W., Xu, H., Liu, R., Xu, X., Xiang, C., Xiong, F. Tags: PublishAheadOfPrint Source Type: research

Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism
Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular diseases (CVD) development. We previously showed that circulating microRNA(miR)-33a/b expression levels were up-regulated in children with familial hypercholesterolaemia (FH). miR-33a/b control cholesterol homoeostasis and recently miR-33b has been demonstrated to directly target the transcription factor ZEB1. The latter acts in a negative feedback-loop with miR-200 family. Our previous studies showed that the ROS-dependent miR-200c up-regulation induces endothelial dysfunction and provokes a ZEB1-dependent a...
Source: Clinical Science - August 15, 2017 Category: Biomedical Science Authors: D'Agostino, M., Martino, F., Sileno, S., Barilla, F., Beji, S., Marchetti, L., Gangi, F. M., Persico, L., Picozza, M., Montali, A., Martino, E., Zanoni, C., Avitabile, D., Parrotto, S., Capogrossi, M. C., Magenta, A. Tags: PublishAheadOfPrint Source Type: research

Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway
Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuro-inflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses anti-oxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly at...
Source: Clinical Science - August 15, 2017 Category: Biomedical Science Authors: Wan, P., Su, W., Zhang, Y., Li, Z., Deng, C., Zhuo, Y. Tags: PublishAheadOfPrint Source Type: research

Cardiovascular susceptibility to in vivo ischemic myocardial injury in male and female rat offspring exposed to prenatal hypoxia
Intrauterine growth restriction following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia. Male offspring exposed to prenatal ...
Source: Clinical Science - August 6, 2017 Category: Biomedical Science Authors: Shah, A., Matsumura, N., Quon, A., Morton, J. S., Dyck, J., Davidge, S. T. Tags: PublishAheadOfPrint Source Type: research

Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial co-infection pneumonia model
Formyl peptide receptor 2 (Fpr2/ALX) coordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the pro-resolving actions of aspirin triggered-RvD1 (AT-RvD1) in an acute co-infection pneumonia model. Co-infection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of co-infected mice, and immunohistochemistry identified prominent Fpr2/AL...
Source: Clinical Science - August 4, 2017 Category: Biomedical Science Authors: Wang, H., Anthony, D., Yatmaz, S., Wijburg, O., Satzke, C., Levy, B., Vlahos, R., Bozinovski, S. Tags: PublishAheadOfPrint Source Type: research

Embryonic stem cell-derived germ cells induce spermatogenesis following transplantation to testis of adult mouse azoospermia model
This study aimed to (a) identify the exogenous factors that allow in vitro differentiation of mouse SSCs from embryonic stem cells (ESCs); (b) evaluate the effects of Sertoli cells on SSCs enrichment; and (c) to assess the success of transplantation using in vitro differentiated SSCs in mouse busulfan-treated azoospermia model. One-day-old embryoid body (EB) received 5 ng/ml BMP4 for 4 days, 3 µM retinoic acid (RA) in STO co-culture (Co-C) system for 7 days and subsequently co-cultured for 2 days with Sertoli cell in the presence or absence of LIF, bFGF and RA composition and in the presence of these factors in the s...
Source: Clinical Science - August 2, 2017 Category: Biomedical Science Authors: Makoolati, Z., Movahedin, M., Forouzandeh-Moghadam, M., Naghdi, M., Koruji, M. Tags: PublishAheadOfPrint Source Type: research

Cardiovascular susceptibility to in vivo ischemic myocardial injury in male and female rat offprint exposed to prenatal hypoxia
Intrauterine growth restriction following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia. Male offspring exposed to prenatal ...
Source: Clinical Science - July 28, 2017 Category: Biomedical Science Authors: Shah, A., Matsumura, N., Quon, A., Morton, J. S., Dyck, J., Davidge, S. T. Tags: PublishAheadOfPrint Source Type: research

LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-{kappa}B signaling
In conclusion, the present study indicates that LILRB4 deficiency promotes atherogenesis, at least partly, through reduced Shp1 phosphorylation, which subsequently enhances the NF-B-mediated inflammatory response. Thus, targeting the "LILRB4-Shp1" axis may be a novel therapeutic approach for atherosclerosis. (Source: Clinical Science)
Source: Clinical Science - July 25, 2017 Category: Biomedical Science Authors: Jiang, Z., Qin, J.-J., Zhang, Y., Cheng, W.-L., Ji, Y.-X., Gong, F.-H., Zhu, X.-Y., Zhang, Y., She, Z.-G., Huang, Z., Li, H. Tags: PublishAheadOfPrint Source Type: research

CX3CR1 modulates the anti-inflammatory activity of hepatic dendritic cells in response to acute liver injury
In this study, we investigated the role of CX3CR1 on mouse HDCs during homeostasis and following acute liver injury. At homeostasis, CX3CR1-expression was detected among CD11b+/CD103- type 2 myeloid HDCs (mHDCs) and these cells were characterized by the production of IL-10.   Mice treatment with the hepatotoxic agent CCl4 up-regulated liver IL-10 expression and stimulated the expansion of CX3CR1+ mHDCs which also showed a more mature phenotype. The absence of CX3CR1 in naïve CX3CR1gfp/gfp mice specifically reduced the CD11b+/IL-10+ mHDCs as compared to CX3CR1-proficient animals (CX3CR1+/gfp).  Following...
Source: Clinical Science - July 24, 2017 Category: Biomedical Science Authors: Sutti, S., Heymann, F., Bruzzi, S., Peusquens, J., Trautwein, C., Albano, E., Tacke, F. Tags: PublishAheadOfPrint Source Type: research

TLR9 is upregulated in human and murine NASH: pivotal role for inflammatory recruitment and cell survival.
Conclusion: Our novel clinical data and studies in over-nutrition models, including those with diabetes and metabolic syndrome, clarify TLR9 as a pro-inflammatory trigger in NASH. This response is mediated via M1-macrophages and neutrophil chemotaxis. (Source: Clinical Science)
Source: Clinical Science - July 7, 2017 Category: Biomedical Science Authors: Mridha, A. R., Haczeyni, F., Yeh, M. M., Haigh, W. G., Ioannou, G. N., Barn, V., Ajamieh, H., Adams, L., Hamdorf, J. M., Teoh, N. C., Farrell, G. C. Tags: PublishAheadOfPrint Source Type: research

Chronic cerebral hypoperfusion alters amyloid-{beta} peptide pools leading to cerebral amyloid angiopathy, microinfarcts and hemorrhages in Tg-SwDI mice
Cerebral hypoperfusion is an early feature of Alzheimer's disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesised that cerebral hypoperfusion promotes the accumulation of amyloid-β (Ab) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Ab peptide pools in a transgenic mouse model of AD (Tg-SwDI) at ...
Source: Clinical Science - June 30, 2017 Category: Biomedical Science Authors: Salvadores, N., Searcy, J. L., Holland, P. R., Horsburgh, K. Tags: PublishAheadOfPrint Source Type: research

Nintedanib, a triple tyrosine kinase inhibitor, attenuates renal fibrosis in chronic kidney disease
Nintedanib (BIBF1120) is a triple kinase inhibitor of platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), vascular endothelial growth factor receptor (VEGFR) and Src family kinase, that has recently been approved by FDA to treat idiopathic pulmonary fibrosis. Whether it affects renal fibrosis remains unknown. Here we demonstrated that administration of nintedanib immediately or 3 days after unilateral ureteral obstruction (UUO) injury and with folic acid injection attenuated renal fibrosis and inhibited activation of renal interstitial fibroblasts. Delayed administration of nintedani...
Source: Clinical Science - June 28, 2017 Category: Biomedical Science Authors: Liu, F., Wang, L., Qi, H., Wang, J., Jiang, w., Wang, Y., Xu, L., Liu, N., Zhuang, S. Tags: PublishAheadOfPrint Source Type: research

AT1-receptor blockade attenuates outward aortic remodeling associated with diet-induced obesity in mice
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as f...
Source: Clinical Science - June 23, 2017 Category: Biomedical Science Authors: Krueger, F., Kappert, K., Foryst-Ludwig, A., Kramer, F., Clemenz, M., Grzesiak, A., Sommerfeld, M., Frese, J. P. B., Greiner, A., Kintscher, U., Unger, T., Kaschina, E. Tags: PublishAheadOfPrint Source Type: research

Nintedanib, a triple tyrosine kinase inhibitor, attenuates renal fibrosis in chronic kidney disease
Nintedanib (BIBF1120) is a triple kinase inhibitor of platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), vascular endothelial growth factor receptor (VEGFR) and Src family kinase, that has recently been approved by FDA to treat idiopathic pulmonary fibrosis. Whether it affects renal fibrosis remains unknown. Here we demonstrated that administration of nintedanib immediately or 3 days after unilateral ureteral obstruction (UUO) injury and with folic acid injection attenuated renal fibrosis and inhibited activation of renal interstitial fibroblasts. Delayed administration of nintedani...
Source: Clinical Science - June 23, 2017 Category: Biomedical Science Authors: Liu, F., Wang, L., Qi, H., Wang, J., Jiang, w., Wang, Y., Xu, L., Liu, N., Zhuang, S. Tags: PublishAheadOfPrint Source Type: research

MiR-223 represents a biomarker in acute and chronic liver injury
Conclusion: MiR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis. (Source: Clinical Science)
Source: Clinical Science - June 23, 2017 Category: Biomedical Science Authors: Schueller, F., Roy, S., Loosen, S. H., Alder, J., Koppe, C., Schneider, A. T., Wandrer, F., Bantel, H., Vucur, M., Mi, Q.-S., Trautwein, C., Luedde, T., Roderburg, C. Tags: PublishAheadOfPrint Source Type: research

Expression of miR-23a induces telomere shortening and is associated with poor clinical outcomes in patients with coronary artery disease
In conclusion, elevated levels of miR-23a play an important role in coronary atherosclerosis via downregulated TRF2, and may provide important prognostic information in patients with CAD. Additionally, aggressive LLT may prevent telomere erosion via downregulated miR-23a. (Source: Clinical Science)
Source: Clinical Science - June 23, 2017 Category: Biomedical Science Authors: Satoh, M., Nasu, T., Takahashi, Y., Osaki, T., Hitomi, S., Morino, Y., Nakamura, M. Tags: PublishAheadOfPrint Source Type: research

MHC class II invariant chain peptide or gamma-delta T cell depletion ameliorates experimental preeclampsia
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia; however, the molecular mechanisms involved are unknown.  We tested the hypothesis that Toll-like receptor activation induces MHC class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause preeclampsia-like features in mice.  Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat preeclampsia-like features in mice.  We then determined tha...
Source: Clinical Science - June 22, 2017 Category: Biomedical Science Authors: Chatterjee, P., Chiasson, V. L., Seerangan, G., De Guzman, E., Milad, M., Bounds, K. R., Gasheva, O., Tobin, R. P., Hatahet, M., Kopriva, S., Jones, K. A., Newell-Rogers, M. K., Mitchell, B. Tags: PublishAheadOfPrint Source Type: research

Reduced platelet count, but no major platelet function abnormalities, are associated with loss of function ATP-binding cassette-1 (ABCA1) gene mutations.
In conclusion, three patients carrying ABCA1 genetic variants had low platelet count, with the lowest values observed in TD, not associated with major alterations in platelet morphology and response to agonists, nor bleeding. (Source: Clinical Science)
Source: Clinical Science - June 20, 2017 Category: Biomedical Science Authors: Minuz, P., Meneguzzi, A., Femia, E. A., Fava, C., Calabria, S., Scavone, M., Benati, D., Poli, G., Zancanaro, C., Calandra, S., Lucchi, T., Cattaneo, M. Tags: PublishAheadOfPrint Source Type: research

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1{Delta}/-mice
DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system . Ercc1/- mice showed...
Source: Clinical Science - June 15, 2017 Category: Biomedical Science Authors: Wu, H., van Thiel, B. S., Bautista-Nino, P. K., Reiling, E., Durik, M., Leijten, F. P. J., Ridwan, Y., Brandt, R. M. C., van Steeg, H., Dolle, M. E. T., Vermeij, W. P., Hoeijmakers, J. H. J., Essers, J., van der Pluijm, I., Danser, A. H. J., Roks, A. J. M Tags: PublishAheadOfPrint Source Type: research