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

MIB1 Mutations Reduce Notch Signaling Activation and Contribute to Congenital Heart Disease
Congenital heart disease (CHD) is one of the most common birth defects in humans, but its genetic etiology remains largely unknown despite decades of research. The Notch signaling pathway plays critical roles in embryonic cardiogenesis. Mind bomb 1 (Mib1) is a vital protein that activates the Notch signaling pathway through promoting ubiquitination, endocytosis and subsequent activation of Notch ligands. Previous studies show that Mib1 knockout in mice completely abolishes Notch signaling, leading to cardiac deformity. However, the function of MIB1 and its potential disease-causing mutations are poorly studied in human CHD...
Source: Clinical Science - October 15, 2018 Category: Biomedical Science Authors: Li, B., Yu, L., Liu, D., Yang, X., Zheng, Y., Gui, Y., Wang, H. Tags: PublishAheadOfPrint Source Type: research

Prevention of Perinatal Nicotine-induced Bone Marrow Mesenchymal Stem Cell Myofibroblast Differentiation by Augmenting the Lipofibroblast Phenotype
Perinatal nicotine exposure drives the differentiation of alveolar lipofibroblasts (LIFs), which are critical for lung injury repair, to myofibroblasts (MYFs), which are the hallmark of chronic lung disease. Bone marrow-derived mesenchymal stem cells (BMSCs) are important players in lung injury repair; however, how these cells are affected with perinatal nicotine exposure and whether these can be preferentially driven to a lipofibroblastic phenotype are not known. We hypothesized that perinatal nicotine exposure would block offspring BMSCs lipogenic differentiation, driving these cells towards a MYF phenotype. Since PPAR a...
Source: Clinical Science - October 11, 2018 Category: Biomedical Science Authors: Sakurai, R., Liu, J., Wang, Y., Torday, J. S., Rehan, V. K. Tags: PublishAheadOfPrint Source Type: research

Novel treatment avenues for uterine leiomyoma: A new implication for Endothelin?
CYR61 (cysteine-rich angiogenic inducer 61), an angiogenic factor whose expression is decreased in fibroids. The aim of this study was to determine if CYR61 secretion in smooth muscle cells is regulated by hypoxia and through the endothelin A (ETA) receptor. Smooth muscle cells from fibroids (fSMC) and the adjacent myometrium smooth muscle cells (mSMC) were extracted from 10 women undergoing hysterectomy for uterine fibroids and cultured with or without 1.0µM of an ETA receptor antagonist for 24hrs under either normal or hypoxic oxygen conditions. Cellular secretion of endothelin-1 (ET-1) and CYR61 were measured via ...
Source: Clinical Science - October 9, 2018 Category: Biomedical Science Authors: Wallace, K., Chatman, K., Johnson, V., Brookins, A., Rushing, J., LaMarca, B. Tags: PublishAheadOfPrint Source Type: research

Degranulation of Gastrointestinal Mast Cells Contributes to Hepatic Ischemia-Reperfusion Injury in Mice
The pathological changes following liver damage, including those caused by ischemia and reperfusion (I/R), are closely related to gastrointestinal dysregulation. Mast cells (MCs) are tissue-resident immune cells abundant in the gastrointestinal system that play diverse roles. In view of the characteristic localization of MCs around the microvasculature, we hypothesized that a stimulus-specific set of mediators released through degranulation of gastrointestinal MCs, which are enriched in hepatic sinusoids via the hepatic system, subsequently participate in associated pathological development within the liver. To elucidate t...
Source: Clinical Science - October 9, 2018 Category: Biomedical Science Authors: He, Z., Li, Y., Ma, S., Yang, M., Ma, Y., Ma, C., Song, J., Yu, T., Zhang, S., Li, J. Tags: PublishAheadOfPrint Source Type: research

Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy
In this study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts. Treatment with 3-MA also abrogated the development of HN in vivo as evidenced by improving renal function, preserving renal tissue architecture, reducing the number of autophagic vacuoles, and decreasing microalbuminuria. Moreover, 3-MA was effective in attenuating renal deposition of...
Source: Clinical Science - October 7, 2018 Category: Biomedical Science Authors: Bao, J., Shi, Y., Tao, M., Liu, N., Zhuang, S., Yuan, W. Tags: PublishAheadOfPrint Source Type: research

Omega-3 Polyunsaturated Fatty Acids Reduce Preterm Labor by Inhibiting Trophoblast Cathepsin S and Inflammasome Activation
In this study, we found that inflammasome-related molecules and IL-1β in trophoblasts were activated by TNF-α derived from lipopolysaccharide-stimulated THP-1 cell-conditioned medium and recombinant TNF-α protein. The results demonstrated that stimulation with TNF-α caused lysosomal rupture in trophoblasts, which accelerated cathepsin S diffusion from lysosomes to the cytosol and activated NLRP1 and AIM2 inflammasomes, thereby increasing IL-1β secretion. Moreover, in response to LPS challenge, TNF-α increased trophoblast cell death and decreased cell viability through inflammasome and cath...
Source: Clinical Science - October 4, 2018 Category: Biomedical Science Authors: Chen, C. Y., Chen, C.-Y., Liu, C.-C., Chen, C.-P. Tags: PublishAheadOfPrint Source Type: research

Early isolated v-lesion may not truly represent rejection of the kidney allograft
Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection,clinical and prognostic significance of early IV (eIV) with negative C4d and donor specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (TCMRV, n=4) and non-rejection histologic findings (n=8...
Source: Clinical Science - October 4, 2018 Category: Biomedical Science Authors: Wohlfahrtova, M., Hruba, P., Klema, J., Novotny, M., Krejcik, Z., Stranecky, V., Honsova, E., Vichova, P., Viklicky, O. Tags: PublishAheadOfPrint Source Type: research

Blebbistatin Modulates Prostatic Cell Growth and Contractility through Myosin II Signaling
Conclusion. Our novel data demonstrates BLEB regulated myosin expression and functional activity. The mechanism involved MLC20 dephosphorylation and altered SMM isoform composition. (Source: Clinical Science)
Source: Clinical Science - October 2, 2018 Category: Biomedical Science Authors: Chen, P., Xu, D.-q., Xu, S.-l., Xiao, H., Wan, S.-h., Wang, X.-h., DiSanto, M. E., Zhang, X.-h. Tags: PublishAheadOfPrint Source Type: research

Human Placental Exosomes in Gestational Diabetes Mellitus Carry a Specific Set of miRNAs Associated with Skeletal Muscle Insulin Sensitivity
There is increasing evidence that miRNAs, which are enriched in nanovesicles called exosomes, are important regulators of gene expression. When compared to normal pregnancies, gestational diabetes mellitus (GDM) is associated with skeletal muscle insulin resistance as well as increased levels of circulating placental exosomes. Here we investigated whether placental exosomes in GDM carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villous (CV) explants from both women with Normal Glucose Tolerant (NGT) and GDM pregnancies. Using miRNA sequencing, we ide...
Source: Clinical Science - September 25, 2018 Category: Biomedical Science Authors: Nair, S., Jayabalan, N., Guanzon, D., Palma, C., Scholz-Romero, K., Elfeky, O., Zuniga, F., Ormazabal, V., Diaz, E., Rice, G. E., Duncombe, G., Jansson, T., McIntyre, H. D., Lappas, M., Salomon, C. Tags: PublishAheadOfPrint Source Type: research

The relationship between habitual dietary sodium intake and RAAS blockade on circulating microparticle levels in type two diabetes.
In this study, we investigated the associations between habitual sodium intake and RAAS blockade on endothelial function by measuring circulating microparticles (MPs) in individuals with T2D.  We conducted a prospective, cross-sectional studyin 74 individuals with T2D. Habitual dietary sodium intake was estimated using the mean of three corrected 24-hour urine sodium excretion measurements (24hUNa). MP subtypes in platelet-free plasma were quantified using flow cytometry.No associations between 24hUNa with levels of endothelial MPs were observed.  Instead, a trend towards higher diabetes related CD36+/CD235a+ MP ...
Source: Clinical Science - September 24, 2018 Category: Biomedical Science Authors: Baqar, S., Liu, D., Lincz, L. F., Kong, Y. W., Jerums, G., Ekinci, E. I. Tags: PublishAheadOfPrint Source Type: research

The downregulation of hsa_circ_0012919, sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4+T cells of SLE
Background: Systemic lupus erythematous (SLE) is an autoimmune disease characterized by production of autoantibodies directed against various autoantigens. But the expression profiles and functions of circRNAs in SLE are still scarce. Objectives: To explore the roles of circRNA in SLE and its potential diagnostic potential in SLE. Methods: SLE patients and healthy control subjects were recruited. CD4+ T cellswere isolated, circRNA microarray analysis were used to screen for circRNA candidate in CD4+ T cells. Expression of DNMT1, CD11a and CD70 and methylation level of CD11a and CD70 were detected after transfecting hsa_cir...
Source: Clinical Science - September 20, 2018 Category: Biomedical Science Authors: Zhang, C., Wang, X., Chen, Y., Wu, Z., Zhang, C., Shi, W. Tags: PublishAheadOfPrint Source Type: research

Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats
In conclusion, the present data indicated that the antioxidant and anti-inflammatory potential of PEDF plays important role in restoring erectile function by inhibition of oxidative stress and TNF-α production. (Source: Clinical Science)
Source: Clinical Science - September 19, 2018 Category: Biomedical Science Authors: Qiao, H., Zhang, Y., Lin, W., Wang, Y.-F., Furdui, C. M., Jiang, Q., Li, X., Long, T., Wang, Y., Qin, D.-n. Tags: PublishAheadOfPrint Source Type: research

Urinary angiotensinogen predicts progressive chronic kidney disease after an episode of experimental acute kidney injury
In this study, we test the utility of urinary angiotensinogen (UAGT) for dynamically evaluating renal structural changes and predicting AKI-CKD progression by using both mild and severe bilateral renal ischemia/reperfusion injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed by kidney architecture restoration, whereas sustained increase in UAGT accompanies by ongoing renal fibrosis after severe AKI. UAGT at day 14-42 correlates with renal fibrosis 84 days after AKI. For predicting fibrosis at day 84, the area under receiver operating characteristics curve of UAGT at day 14 is 0.81. Persistent el...
Source: Clinical Science - September 17, 2018 Category: Biomedical Science Authors: Cui, S., Wu, L., Feng, X., Su, H., Zhou, Z., Luo, W., Su, C., Li, Y., Shi, M., Yang, Z., Cao, W. Tags: PublishAheadOfPrint Source Type: research

Local Cyclical Compression Modulates Macrophage Function In Situ and Alleviates Immobilization-Induced Muscle Atrophy
Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to ageing. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary life style, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of...
Source: Clinical Science - September 12, 2018 Category: Biomedical Science Authors: Saitou, K., Tokunaga, M., Yoshino, D., Sakitani, N., Maekawa, T., Ryu, Y., Nagao, M., Nakamoto, H., Saito, T., Kawanishi, N., Suzuki, K., Ogata, T., Makuuchi, M., Takashima, A., Sawada, K., Kawamura, S., Nakazato, K., Kouzaki, K., Harada, I., Ichihara, Y. Tags: PublishAheadOfPrint Source Type: research

Targeting Amino Acids Metabolic Profile to Identify Novel Metabolic Characteristics in Atrial Fibrillation
Conclusion: By utilizing non-target metabolic profile surveys, we have found a number of altered amino acids, which exhibit diagnostic value for AF. Enhanced amino acids correlation network further identified AF as a metabolism disorder. (Source: Clinical Science)
Source: Clinical Science - September 6, 2018 Category: Biomedical Science Authors: She, J., Guo, M., Li, H., Liu, J., Liang, X., Liu, P., Zhou, B., Liu, S., Deng, Y., Lou, B., Sun, C., Yuan, Z., Wu, Y. Tags: PublishAheadOfPrint Source Type: research

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
The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP). uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR). Results: CMV viremia was detected in 79.9% of the pa...
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
Rho-kinase has relevant functions in blood pressure modulation and cardiovascular remodeling. Rho-kinase activity is determined in circulating leukocytes measuring phosphorylation of its target myosin-phosphatase-target-subunit-1 (MYPT1) but its relationship with Rho-kinase activity in the myocardium and in vasculature in hypertension has not been evaluated. The aim was to determine the degree of association between Rho-kinase cascade activation in circulating leukocytes with cardiac and aortic Rho-kinase pathway activation in a model of hypertension and to analyze it with a cause effect perspective. Hypertensive DOCA...
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 (D...
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

Probiotic Lactobacillus paracasei HII01 protects rats against obese-insulin resistance-induced kidney injury and impaired renal organic anion transporter 3 (Oat3) function
In conclusion, probiotic supplementation alleviated kidney inflammation, ER stress, and apoptosis, leading to improved kidney function and renal Oat3 function in obese rats.  These benefits involve the attenuation of hyperlipidemia, systemic inflammation and insulin resistance.  This study also suggested the idea of remote sensing and signaling system between gut and kidney by which probiotic might facilitate renal handling of gut microbiota products through the improvement of Oat3 function. (Source: Clinical Science)
Source: Clinical Science - July 6, 2018 Category: Biomedical Science Authors: Wanchai, K., Yasom, S., Tunapong, W., Chunchai, T., Eaimworawuthikul, S., Thiennimitr, P., Chaiyasut, C., Pongchaidecha, A., Chatsudthipong, V., Chattipakorn, S., Chattipakorn, N., Lungkaphin, A. Tags: PublishAheadOfPrint Source Type: research

Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways
Rhinovirus (RV) infection is involved in acute exacerbations of asthma and chronic obstructive pulmonary disease. RV primarily infects upper and lower airway epithelium. Immunoproteasomes (IP) are proteolytic machineries with multiple functions including the regulation of MHC class I antigen processing during viral infection. However, the role of IP in RV infection has not been explored. We sought to investigate the expression and function of IP during airway RV infection. Primary human tracheobronchial epithelial (HTBE) cells were cultured at air-liquid interface and treated with RV16, RV1B or IFN-l in the absence or pres...
Source: Clinical Science - July 6, 2018 Category: Biomedical Science Authors: Dimasuay, K. G., Sanchez, A., Schaefer, N., Polanco, J., Ferrington, D. A., Chu, H. W. Tags: PublishAheadOfPrint Source Type: research

Adrenergic- and non-adrenergically-mediated human adipose tissue lipolysis during acute exercise and exercise training
Obesity-related adipose tissue dysfunction, in particular subcutaneous adipose tissue (SCAT) lipolysis, is characterized by catecholamine resistance and impaired ANP responsiveness. It remains unknown whether exercise training improves (non-)adrenergically-mediated lipolysis in metabolically compromised conditions. We investigated the effect of local combined α-/β-adrenoceptor blockade on abdominal SCAT lipolysis in lean insulin sensitive (IS, n=10), obese IS (n=10) and obese insulin resistant (IR, n=10) men. Obese men participated in a 12-week exercise training intervention to determine the effects on SCAT lipo...
Source: Clinical Science - July 6, 2018 Category: Biomedical Science Authors: Verboven, K., Stinkens, R., Hansen, D., Wens, I., Frederix, I., Eijnde, B. O., Jocken, J. W., Goossens, G. H., Blaak, E. E. Tags: PublishAheadOfPrint Source Type: research

Validity of predictive equations for resting metabolic rate in healthy humans
Background: There are several predictive equations for estimating resting metabolic rate (RMR) in healthy humans. Concordance of these equations against measured RMR is variable, and often dependent on the extent of RMR. Part of the discrepancy may lie on an insufficient accuracy of metabolic carts, but this accuracy can be improved through a correction procedure. Objective: To determine the validity of predictive RMR equations by comparing them against measured and corrected (i.e. the reference) RMR. Methods: In 69 healthy volunteers (29 males/40 females; 32±8 y old; BMI 25.5±3.8 kg/m2), RMR was me...
Source: Clinical Science - July 2, 2018 Category: Biomedical Science Authors: Galgani, J. E., Castro-Sepulveda, M., Perez-Luco, C., Fernandez-Verdejo, R. Tags: PublishAheadOfPrint Source Type: research

The renal protect function of erythropoietin after releasing of bilateral ureteral obstruction in a rat model
In conclusion, EPO could promote the recovery of renal function and AQP2 expression in BUO-R rats which may partially associate with its anti-inflammation effect. (Source: Clinical Science)
Source: Clinical Science - June 29, 2018 Category: Biomedical Science Authors: Ren, C. C., Wang, Q. W., Lu, Y. T., Wang, Y., Zhu, W., Zhang, G. X., Xie, J. F., Zhang, T., Wu, J. W., Jia, Z. M., Su, Z. Q., Wen, J. G. Tags: PublishAheadOfPrint Source Type: research

Adenylyl cyclase 6 is required for maintaining acid-base homeostasis
In conclusion, AC6 is required for maintaining normal acid-base homeostasis and energy expenditure. Under baseline conditions renal AC6 is redundant for acid-base balance but becomes important under alkaline conditions. (Source: Clinical Science)
Source: Clinical Science - June 25, 2018 Category: Biomedical Science Authors: Poulsen, S. B., Marin De Evsikova, C., Murali, S. K., Praetorius, J., Chern, Y., Fenton, R. A., Rieg, T. Tags: PublishAheadOfPrint Source Type: research

Amino acid and lipid associated plasma metabolomic patterns are related to healthspan indicators with aging in humans
Advancing age is associated with impairments in numerous physiological systems, leading to an increased risk of chronic disease and disability, and reduced healthspan (the period of high functioning healthy life). The plasma metabolome is thought to reflect changes in the activity of physiological systems that influence healthspan. Accordingly, we utilized an LC-MS metabolomics analysis of plasma collected from healthy young and older individuals to characterize global changes in small molecule abundances with age. Using a weighted gene correlation network analysis, similarly expressed metabolites were grouped into modules...
Source: Clinical Science - June 18, 2018 Category: Biomedical Science Authors: Johnson, L. C., Martens, C. R., Santos-Parker, J. R., Bassett, C. J., Strahler, T. R., Cruickshank-Quinn, C., Reisdorph, N., McQueen, M. B., Seals, D. R. Tags: PublishAheadOfPrint Source Type: research

HMGB1-induced autophagy facilitates hepatic stellate cells activation: a new pathway in liver fibrosis
High-mobility group box-1 (HMGB1) plays a context-dependent role in autophagy, which is required for hepatic stellate cells (HSCs) activation. However, the significance of HMGB1-induced HSCs autophagy in liver fibrosis has not been elucidated. Here, we first documented an enrichment of peripheral and intra-hepatic HMGB1 signal in hepatitis B virus (HBV)-related liver fibrosis progression, and presented the direct evidence of anatomic proximity of HMGB1 with a-SMA (a marker for HSCs activation) in cirrhotic liver specimens. Then, we demonstrated the autophagy-inducing effects by serum-sourced HMGB1 in both primary murine HS...
Source: Clinical Science - June 15, 2018 Category: Biomedical Science Authors: Li, J., Zeng, C., Zheng, B., Liu, C., Tang, M., Jiang, Y., Chang, Y., Song, W., Wang, Y., Yang, C. Tags: PublishAheadOfPrint Source Type: research

Central administration of TRV027 improves baroreflex sensitivity and vascular reactivity in spontaneously hypertensive rats
This study evaluates the effect of central infusion of TRV027 on arterial pressure (AP), autonomic function, baroreflex sensitivity and peripheral vascular reactivity. Spontaneously hypertensive (SH) and Wistar Kyoto (WKY) rats were treated with TRV027 for 14 days (20 ng/hour) delivered to the lateral ventricle via osmotic minipumps. Mechanistic studies were performed in HEK293T cells co-transfected with AT1R and angiotensin converting enzyme type 2 (ACE2) treated with TRV027 (100 nM) or Ang-II (100 nM). TRV027 infusion in SHR reduced AP (~20 mmHg, p
Source: Clinical Science - June 14, 2018 Category: Biomedical Science Authors: Carvalho-Galvao, A., Ogunlade, B., Xu, J., Silva-Alves, C. R. A., Mendes-Junior, L. G., Guimaraes, D. D., Cruz, J. C., Queiroz, T. M., Balarini, C. M., Braga, V. A., Filipeanu, C. M., Lazartigues, E., Franca-Silva, M. S. Tags: PublishAheadOfPrint Source Type: research

The preventive and therapeutic implication for renal fibrosis by targeting TGF-{beta}/Smad3 signaling
In conclusion, results from this study suggest that targeting Smad3 may be a specific and effective therapy for renal fibrosis. (Source: Clinical Science)
Source: Clinical Science - June 6, 2018 Category: Biomedical Science Authors: Zhang, Y., Meng, X.-M., Huang, X.-R., Lan, H. Y. Tags: PublishAheadOfPrint Source Type: research

Impact of PEGylation on the mucolytic activity of recombinant human deoxyribonuclease I in cystic fibrosis sputum
Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs a...
Source: Clinical Science - June 5, 2018 Category: Biomedical Science Authors: Guichard, M.-J., Kinoo, D., Aubriot, A.-S., Bauwens, N., Gougue, J., Vermeulen, F., Lebecque, P., Leal, T., Vanbever, R. Tags: PublishAheadOfPrint Source Type: research

Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction
In conclusions, GW8510 can reverses gemcitabine resistance in LSCC cells through RRM2 downregulation-mediated autophagy induction, and GW850 may be a promising therapeutic agent against LSCC as it combined with gemcitabine. (Source: Clinical Science)
Source: Clinical Science - May 31, 2018 Category: Biomedical Science Authors: Chen, P., Wu, J.-N., Shu, Y., Jiang, H.-G., Zhao, X.-H., Qian, H., Chen, K., Lan, T., Chen, C.-G., Li, J. Tags: PublishAheadOfPrint Source Type: research

Prorenin independently causes hypertension and renal and cardiac fibrosis in cyp1a1-prorenin transgenic rats
In this study, a transgenic, inducible, hepatic prorenin-overexpressing rat model was generated and the effect of prorenin in organ injury was examined. Four groups of rats (cyp1a1 prorenin transgenic male and female rats and nontransgenic littermates) were assigned to receive a diet containing 0.3% of the transgene inducer indole-3-carbinol (I3C) for 4 weeks. Plasma prorenin concentration was increased and MAP increased from 80±18 to 138±17 (mmHg), whereas renal prorenin/renin protein expression was unchanged, in transgenic rats fed with I3C diet. The intact prorenin, not renin, in plasma and urine samples w...
Source: Clinical Science - May 30, 2018 Category: Biomedical Science Authors: Zhou, G., Wu, J., Gu, C., Wang, B., Abel, E. D., Cheung, A. K., Huang, Y. Tags: PublishAheadOfPrint Source Type: research

Targeted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance
This study suggested that COX-2-mediated MIF secretion through NFB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity. (Source: Clinical Science)
Source: Clinical Science - May 17, 2018 Category: Biomedical Science Authors: Chan, P.-C., Wu, T.-N., Chen, Y.-C., Lu, C.-H., Wabitsch, M., Tian, Y.-F., Hsieh, P.-S. Tags: PublishAheadOfPrint Source Type: research

High {alpha}-Tocopherol dosing increases lipid metabolism by changing redox state in damaged rat gastric mucosa and liver after ethanol treatment
In conclusion, this study shows for the first time the role of lipid metabolism in the adaptive cell gastric mucosa changes that drive proliferation after a chronic insult. Moreover, α-tocopherol increased gastric mucosa utilization of palmitic acid associated with energy production. These events could be associated with its antioxidant properties in coordination with regulation of genes and cell pathways, including changes in the cell NAD/NADH redox state. (Source: Clinical Science)
Source: Clinical Science - May 17, 2018 Category: Biomedical Science Authors: Olguin-Martinez, M., Hernandez-Espinosa, D. R., Hernandez-Munoz, R. Tags: PublishAheadOfPrint Source Type: research