Exacerbated metabolic changes in skeletal muscle of sickle cell mice submitted to an acute ischemia - reperfusion paradigm
Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises. While there are several metabolic abnormalities potentially associated with muscular ischemia - reperfusion cycles which could be harmful in the context of SCD, the metabolic consequences of such events are still unknown. Ten controls (HbAA), 13 heterozygous (HbAS) and 10 homozygous (HbSS) SCD mice were submitted to a standardized protocol of rest - ischemia - reperfusion of the right leg during which ATP, phosphocreatine and inorganic phosphate concentrations as well as intramuscular pH were measured using phosphorous magnetic resonance spectrosc...
Source: Clinical Science - September 5, 2018 Category: Biomedical Science Authors: Chatel, B., Messonnier, L. A., Vilmen, C., Bernard, M., Pialoux, V., Bendahan, D. Tags: PublishAheadOfPrint Source Type: research

TSC1 deletion in fibroblasts alleviates lipopolysaccharide-induced acute kidney injury
Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in inflammation, but its involvement in septic acute kidney injury (AKI) has not been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of TSC1, an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1–/–) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 and p-JNK were upregulated in Fibro-TSC1–/– renal fibroblasts after LPS challenge. Rapamycin, an mTOR...
Source: Clinical Science - September 5, 2018 Category: Biomedical Science Authors: Shen, J., Cui, Z.-K., Yao, F., Li, K., Zhang, Y., Chen, Z., Zhou, Y., Xu, S., Zhang, Y., Jiang, W., Zhang, H., Tan, K., Liu, A., Bai, X. Tags: PublishAheadOfPrint Source Type: research

A high level of urinary retinol-binding protein is associated with cytomegalovirus infection in kidney transplantation
Conclusions: CMV viremia was associated with high uRBP levels, which represent a profile of proximal tubule injury, and the dynamic performance of uRBP after treatment was associated with long-term kidney graft function. (Source: Clinical Science)
Source: Clinical Science - August 31, 2018 Category: Biomedical Science Authors: Requiao-Moura, L. R., Matos, A. C. C., Ozaki, K. S., Camara, N. O. S., Pacheco-Silva, A. Tags: PublishAheadOfPrint Source Type: research

B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats
In conclusion, BNP prevents postnatal DA closure by both vasodilation and anti-remodeling through the cGMP pathway. The mechanisms underlying anti-remodeling effects include anti-proliferation and anti-migration, with attenuation of mitochondrial ROS production and intracellular calcium and ERK1/2 signaling. Therefore, the BNP/cGMP pathway can be a promising therapeutic target for clinical management of DA patency. (Source: Clinical Science)
Source: Clinical Science - August 17, 2018 Category: Biomedical Science Authors: Yeh, J.-L., Wu, J.-R., Wu, B.-N., Yang, S.-F., Dai, Z.-K., Liou, S.-F., Hsu, J.-H. Tags: PublishAheadOfPrint Source Type: research

Proteomic Analysis of Exosomes Reveals an Association between Cell Invasiveness and Exosomal Bioactivity on Endothelial and Mesenchymal Cell Migration In-Vitro
In this study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high=SKOV-3 and low=OVCAR-3) by differential and buoyant density centrifugation and characterized using nanoparticle tracking analysis, western blot and electron microscopy. Exosome secretion was positively correlated with invasiveness of releasing cells. Proteomic analyses identified common and unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology analyses revealing that these exosomes are involved in the regulation of ce...
Source: Clinical Science - August 17, 2018 Category: Biomedical Science Authors: Sharma, S., Alharbi, M., Kobayashi, M., Lai, A., Guanzon, D., Zuniga, F., Ormazabal, V., Palma, C., Scholz-Romero, K., Rice, G. E., Hooper, J. D., Salomon, C. Tags: PublishAheadOfPrint Source Type: research

The relevance of ceramides and their synthesizing enzymes for multiple sclerosis
In conclusion, our results indicate that ceramide metabolism is linked to G-CSF signaling in multiple sclerosis. (Source: Clinical Science)
Source: Clinical Science - August 17, 2018 Category: Biomedical Science Authors: Kurz, J., Brunkhorst, R., Foerch, C., Blum, L., Henke, M., Gabriel, L., Ulshofer, T., Ferreiros, N., Parnham, M. J., Geisslinger, G., Schiffmann, S. Tags: PublishAheadOfPrint Source Type: research

Mechanical Stresses Induce Paracrine Beta-2 Microglobulin from Cardiomyocytes to Activate Cardiac Fibroblasts through Epidermal Growth Factor Receptor
This study suggests β2M is a paracrine pro-fibrotic mediator and associated with cardiac dysfunction in response to pressure overload. (Source: Clinical Science)
Source: Clinical Science - August 2, 2018 Category: Biomedical Science Authors: Li, Y., Zhang, X., Li, L., Wang, X., Chen, Z., Wang, X., Wang, Y., Kang, L., Ye, Y., Jia, J., Zhang, G., Yang, C., Yuan, J., Zhou, J., Ge, J., Gong, H., Zou, Y. Tags: PublishAheadOfPrint Source Type: research

Rho kinase activation in circulating leukocytes is related to hypertensive myocardial remodeling
In conclusion, in this hypertension model, Rho-kinase and its pathway activation determined in circulating leukocytes reflects the activation of this pathway in the myocardium and in the aortic wall and is significantly related to myocardial remodeling  (hypertrophy, fibrosis and inflammation). (Source: Clinical Science)
Source: Clinical Science - July 31, 2018 Category: Biomedical Science Authors: Ocaranza, M. P., Fierro, C., Jalil, J. E., Jackeline, M., Gonzalez, L., Molina, C., Mancilla, C. Tags: PublishAheadOfPrint Source Type: research

Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury
Altered cardiac mitochondrial dynamics with excessive fission is a predominant cause of cardiac dysfunction during ischemia-reperfusion (I/R) injury.  Although pre-ischemic inhibition of mitochondrial fission has been shown to improve cardiac function in I/R injury, the effects of this inhibitor given at different time-points during cardiac I/R injury are unknown.  Fifty Male Wistar rats were subjected to sham and cardiac I/R injury.  For cardiac I/R injury, rats were randomly divided into pre-ischemia, during-ischemia and upon onset of reperfusion group.  A mitochondrial fission inhibitor, Mdivi-1 (1.2...
Source: Clinical Science - July 31, 2018 Category: Biomedical Science Authors: Maneechote, C., Palee, S., Kerdphoo, S., Jaiwongkam, T., Chattipakorn, S. C., Chattipakorn, N. Tags: PublishAheadOfPrint Source Type: research

Occurrence and Regression of BK Polyomavirus Associated Carcinoma: A Clinical and Next Generation Sequencing Study
In conclusion, we propose that integration of the BKPyV genome is closely related to oncogenesis in this patient; while oncogenesis occurred when host immunity was impaired, recovery of the patient's native immunity effectively curbed viral replication and eliminated the metastatic lesions. (Source: Clinical Science)
Source: Clinical Science - July 19, 2018 Category: Biomedical Science Authors: Fu, F., Deng, W., Yu, S., Liu, Y., Yu, L., Liu, R., Lang, J., Geng, D., Geng, J., Li, J., Huang, G., Luo, M., Xiong, F., Wu, C.-L., Miao, Y. Tags: PublishAheadOfPrint Source Type: research

Sex-dependent expression of brain medullary MAP and PI3 kinases in adult sheep with antenatal betamethasone exposure
Antenatal betamethasone (BM) therapy for women in jeopardy of premature delivery accelerates the lung development in preterm infants and reduces infant mortality rates, but may induce early programming events with chronic cardiovascular consequences. In a sheep model of fetal programming, in utero BM-exposed (BMX) offspring as adults exhibit elevated mean arterial pressure (MAP), decreased baroreflex sensitivity (BRS) for control of heart rate and insulin resistance accompanied by dysregulation of the brain renin-angiotensin system (RAS).  However, the status of signaling mechanisms in the brain dorsomedial medulla ...
Source: Clinical Science - July 19, 2018 Category: Biomedical Science Authors: Hendricks, A. S., Shaltout, H. A., Westwood, B. M., Chappell, M. C., Diz, D. I. Tags: PublishAheadOfPrint Source Type: research

Apoptosis signal-regulating kinase 1 (ASK1) inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease (COPD).
Increased airway smooth muscle (ASM) mass is observed in COPD which is correlated with disease severity and negatively impact lung function. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase  activated by various stress stimuli, including reactive oxygen species, tumor necrosis factor-α, and lipopolysaccharide and is known to regulate cell proliferation. ASM cells from COPD patients are hyper-proliferative to mi...
Source: Clinical Science - July 13, 2018 Category: Biomedical Science Authors: Eapen, M. S., Kota, A., Vindin, H., McAlinden, K. D., Xenaki, D., Oliver, B. G., Deshpande, D. A., Sohal, S. S., Sharma, P. Tags: PublishAheadOfPrint Source Type: research

A Preventive Injection of Endothelial Progenitor Cells Prolongs Lifespan in Stroke-prone Spontaneously Hypertensive Rats
In conclusion, a single preventive injection of EPCs prolonged the lifespan of SHR-SP, and protected against cerebral ischemic injury for at least seven weeks. It is implied that EPC injection might be a promising candidate for a preventive role in patients at high risk for stroke. (Source: Clinical Science)
Source: Clinical Science - July 13, 2018 Category: Biomedical Science Authors: Peng, C., Dong, X.-H., Liu, J.-L., Tao, Y.-L., Xu, C.-F., Wang, L.-P., Liu, C.-L., Su, D.-F., Tao, X., Zhang, C., Chen, A. F., Xie, H.-H. Tags: PublishAheadOfPrint Source Type: research

LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis
Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage [CD45, TER-119, CD324, CD31, LYVE-1, and CD146]-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Among several genes upregulated in the FACS-sorted myo...
Source: Clinical Science - July 13, 2018 Category: Biomedical Science Authors: Enomoto, Y., Matsushima, S., Shibata, K., Aoshima, Y., Yagi, H., Meguro, S., Kawasaki, H., Kosugi, I., Fujisawa, T., Enomoto, N., Inui, N., Nakamura, Y., Suda, T., Iwashita, T. Tags: PublishAheadOfPrint Source Type: research

Differential long noncoding RNA expressions in peripheral blood mononuclear cells for detection of acute ischemic stroke
Conclusions The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method. (Source: Clinical Science)
Source: Clinical Science - July 11, 2018 Category: Biomedical Science Authors: Deng, Q.-W., Li, S., Wang, H., Sun, H.-L., Zuo, L., Gu, Z.-T., Lu, G., Sun, C.-Z., Zhang, H.-Q., Yan, F.-L. Tags: PublishAheadOfPrint Source Type: research