Heme oxygenase-1 induction by hemin prevents oxidative stress-induced acute cholestasis in the rat
We previously demonstrated in in vitro and ex vivo models that physiological concentrations of unconjugated bilirubin prevent oxidative stress (OS)-induced hepatocanalicular dysfunction and cholestasis. Here, we aimed to ascertain, in the whole rat, whether a similar cholestatic OS injury can be counteracted by heme oxygenase-1 (HO-1) induction that consequently elevates endogenous bilirubin (BR) levels. This was achieved through the administration of hemin, an inducer of HO-1, the rate-limiting step in BR generation. We found that BR peaked between 6-8 h after hemin administration. During this time period, HO-1 induct...
Source: Clinical Science - December 11, 2018 Category: Biomedical Science Authors: Martin, P. L., Ceccatto, P. L., Razori, M. V., Frances, D. E., Arriaga, S. M., Pisani, G. B., Martinez, A. I., Sanchez Pozzi, E. J., Roma, M. G., Basiglio, C. L. Tags: PublishAheadOfPrint Source Type: research

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis
In this study, we report the identification of a heterozygous nonsense PODXL mutations (Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared to those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human ...
Source: Clinical Science - December 6, 2018 Category: Biomedical Science Authors: Lin, F.-J., Yao, L., Hu, X.-Q., Bian, F., Ji, G., Jiang, G.-R., Gale, D. P., Ren, H.-Q. Tags: PublishAheadOfPrint Source Type: research

GPR120 protects lipotoxicity-induced pancreatic beta-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation
G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic beta cells remains unclear. To explore the potential link between GPR120 and beta-cell function, its agonist DHA and GSK137647AS were used in palmitic acid (PA)-induced pancreatic beats-cell dysfunction, coupled with GPR120 KD in MIN6 cells and GPR120 KO mice to identify the underlying signalling pathways. In vitro and ex vivo treatments of MIN6 cells and islets isolated from WT mice with DH and GSK restored pancreatic PDX1 expression...
Source: Clinical Science - December 6, 2018 Category: Biomedical Science Authors: Wang, Y., Xie, T., Zhang, D., Leung, P. S. Tags: PublishAheadOfPrint Source Type: research

Functional Cardiac Orexin Receptors: Role of Orexin-B/Orexin 2 Receptor in Myocardial Protection
In this study we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative RT-PCR, immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors. In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, D-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific OX1R antagonist (SB-408124) did not alter the responsiveness of OR-B. Treat...
Source: Clinical Science - November 22, 2018 Category: Biomedical Science Authors: Patel, V., Karteris, E., Chen, J., Kyrou, I., Mattu, H. S., Dimitriadis, G. K., Rodrigo, G., Antoniades, C., Antonopoulos, A., Tan, B. K., Hillhouse, E. W., Ng, A., Randeva, H. Tags: PublishAheadOfPrint Source Type: research

Type 3 innate lymphoid cell (ILC3): a new player in liver fibrosis progression
This study was designed to determine the roles of ILC3 in liver fibrosis. By flow cytometry, we documented increased frequencies of peripheral ILC3 (Lin-CD127+CD117+CD294- lymphocytes) in patients, especially at the advanced stage of hepatitis B virus (HBV)-related chronic liver diseases, and demonstrated their correlations with disease progression. The in vitro fibrogenic effects by ILC3 were determined by co-culture experiments with LX-2 [a human hepatic stellate cell (HSC) line]. The data indicate that pathogenic ILC3 can directly promote LX-2 fibrogenesis in non-contact manners by producing interleukin (IL)-17A and I...
Source: Clinical Science - November 20, 2018 Category: Biomedical Science Authors: Wang, S., Li, J., Wu, S.-d., Cheng, L., Shen, Y., Ma, W., She, W., Yang, C., Wang, J., Jiang, W. Tags: PublishAheadOfPrint Source Type: research

Changes in cell fate determine the regenerative and functional capacity of the developing kidney before and after release of obstruction
Congenital obstructive nephropathy is a major cause of chronic kidney disease in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud epithelium and podocytes using Foxd1Cre , Six2Cre , HoxB7Cre and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice. Persistent obstruction leads to a significant loss of tubular epithelium, r...
Source: Clinical Science - November 15, 2018 Category: Biomedical Science Authors: Nagalakshmi, V. K., Li, M., Shah, S., Gigliotti, J. C., Klibanov, A. L., Epstein, F. H., Chevalier, R. L., Gomez, R. A., Sequeira Lopez, M. L. S. Tags: PublishAheadOfPrint Source Type: research

Color Spectrographic Respiratory Monitoring from the External Ear Canal
In this study we describe the use of color spectrographic analysis of breathing sounds recorded from the external ear canal as a candidate technology to meet this need. A miniature electret microphone was modified with the addition of an adapter to allow it to be placed comfortably in the external ear canal. The amplified signal was then connected to a real-time color spectrogram program running on a laptop personal computer utilizing the Windows operating system.  Based on the results obtained, we hypothesize that the real-time display of color spectrogram breathing patterns locally or at a central monitoring station...
Source: Clinical Science - November 12, 2018 Category: Biomedical Science Authors: Jafarian, K., Hassani, K., Doyle, D. J., Niakan Lahiji, M., Moradi Moghaddam, O., Saket, A., Majidi, M., Izadi, F. Tags: PublishAheadOfPrint Source Type: research

Inhibitory effects of vasostatin-1 against atherogenesis
This study provided the first evidence that vasostatin-1 may serve as a novel therapeutic target for atherosclerosis. (Source: Clinical Science)
Source: Clinical Science - November 6, 2018 Category: Biomedical Science Authors: Sato, Y., Watanabe, R., Uchiyama, N., Ozawa, N., Takahashi, Y., Shirai, R., Sato, K., Mori, Y., Matsuyama, T.-a., Ishibashi-Ueda, H., Hirano, T., Watanabe, T. Tags: PublishAheadOfPrint Source Type: research

Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes
In this study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with longstanding Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes.  Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology. (Source: Clinical Science)
Source: Clinical Science - November 6, 2018 Category: Biomedical Science Authors: Mahapatra, G., Smith, S. C., Hughes, T. M., Wagner, B., Maldjian, J. A., Freedman, B. I., Molina, A. J. A. Tags: PublishAheadOfPrint Source Type: research

Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker
Early recognition of vulnerable carotid plaques could help identifying patients at high stroke risk, who may benefit of earlier revascularization. Nowadays, different biomarkers of plaque instability have been unravelled, among these microRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two microRNAs involved in atherosclerosis progression. The goal of the...
Source: Clinical Science - November 2, 2018 Category: Biomedical Science Authors: Magenta, A., Sileno, S., D'Agostino, M., Persiani, F., Beji, S., Paolini, A., Camilli, D., Platone, A., Capogrossi, M. C., Furgiuele, S. Tags: PublishAheadOfPrint Source Type: research

Gestational diabetes alters microRNA signatures in human feto-placental endothelial cells depending on fetal sex
MicroRNAs (miRNAs), small non-coding RNAs, have emerged as important, epigenetic regulators of endothelial function. Metabolic disturbances such as diabetes alter miRNA expression. In adults the miRNA transcriptome as well as endothelial function differ between the sexes. Here we hypothesized that metabolic disturbances associated with gestational diabetes (GDM) alter miRNA signatures in feto-placental endothelial cells (fpEC), dependent on fetal sex. We isolated human primary fpEC after normal and GDM-complicated pregnancies with male and female neonates and screened for differential miRNA expression using next generation...
Source: Clinical Science - November 2, 2018 Category: Biomedical Science Authors: Strutz, J., Cvitic, S., Hackl, H., Kashofer, K., Appel, H. M., Thuringer, A., Desoye, G., Koolwijk, P., Hiden, U. Tags: PublishAheadOfPrint Source Type: research

Alterations in vascular function by syncytiotrophoblast extracellular vesicles via LOX-1 in mouse uterine arteries
Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function, however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via LOX-1, a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the AT-1 receptor for angiotensin II. We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses. Uterine arteries from pregnant control (C5...
Source: Clinical Science - October 23, 2018 Category: Biomedical Science Authors: Spaans, F., Quon, A., Rowe, S. R., Morton, J. S., Kirschenman, R., Sawamura, T., Tannetta, D. S., Sargent, I. L., Davidge, S. T. Tags: PublishAheadOfPrint Source Type: research

Insulin reverses the major portal hypertension-related derangements in rats with liver cirrhosis and diabetes
In conclusion, diabetes aggravated hemodynamic derangements, mesenteric angiogenesis and collaterals in the cirrhotic rats, which were mostly ameliorated by insulin. Further clinical investigations are warranted. (Source: Clinical Science)
Source: Clinical Science - October 22, 2018 Category: Biomedical Science Authors: Hsin, I.-F., Huang, H.-C., Chang, C.-C., Hsu, S.-J., Lee, F.-Y., Huo, T.-I., Chuang, C.-L., Hou, M.-C., Lee, S.-D. Tags: PublishAheadOfPrint Source Type: research

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease.
Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (class II-III) and db/db mice compared to the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol-regulatory element binding protein-1 (SREBP-1) was clearly upregulated, w...
Source: Clinical Science - October 22, 2018 Category: Biomedical Science Authors: Yang, W., Luo, Y., Yang, S., Zeng, M., Zhang, S., Liu, J., Han, Y., Liu, Y., Zhu, X., Wu, H., Liu, F., Sun, L., Xiao, L. Tags: PublishAheadOfPrint Source Type: research

MKP2 inhibits TGF-{beta}1-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells through a JNK-dependent pathway
Epithelial-to-mesenchymal transition (EMT) is a phenotypic conversion that plays a crucial role in renal fibrosis leading to chronic renal failure. Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate the MAP kinase pathway involved in transforming growth factor-β1(TGF-β1)-induced EMT. However, the function of MKP2 in the regulation of EMT and the underlying mechanisms are still largely unknown. In the present study, we detected the expression of MKP2 in an animal model of renal fibrosis and evaluated the potential role of MKP2 in tubular EMT induced by TGF-...
Source: Clinical Science - October 15, 2018 Category: Biomedical Science Authors: Li, Z., Liu, X., Tian, F., Li, J., Wang, Q., Gu, C. Tags: PublishAheadOfPrint Source Type: research