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...
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
This study supports use of molecular methods when interpreting kidney allograft biopsy findings. (Source: Clinical Science)
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 conclusion, lower sodium intake is associated with higher circulating procoagulant MPs but not with evidence of endothelial dysfunction in individuals with T2D. (Source: Clinical Science)
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
Conclusion:Hsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the ceRNA for miR-125a-3p. (Source: Clinical Science)
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
