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
<span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">Nintedanib (BIBF1120) is a triple kinase inhibitor</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> of </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times Ne...
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 show...
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
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<5.0%, T2DM-non-NAFL) group for further analysis.IHL was increased in NAFL and T2DM+NAFL (p<0.050 vs. CON and T2DM-non-NAFL). Adipose ti...
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 wi...
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
