Antifibrotic effects of cyclosporine A on TGF-{beta}1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1{alpha} [Research]
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1&...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura, H., Yoshino, I., Tatsumi, K., Murayama, T. Tags: Research Source Type: research
Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression [Research]
Homozygous tau knockout (Mapt–/–) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/–) pups, but not a complete loss of tau in the Mapt–/– litte...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang, G., Li, Y., Jiang, B., Cai, H., Lin, X. Tags: Research Source Type: research
Caffeine preferentially protects against oxygen-induced retinopathy [Research]
Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L., Chen, J.-F. Tags: Research Source Type: research
miR-191 suppresses angiogenesis by activation of NF-{kappa}B signaling [Research]
In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR-191m–transfected mouse aortic rings was significantly reduced when compared with controls. Transfection with miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti- and proangiogenic activities of miR-191m and -191i were further demonstrated in vivo. Additional molecular biologic analyses revealed that miR-191m activat...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. Tags: Research Source Type: research
KCa1.1 channels regulate {beta}1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes [Research]
Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) isolated from the synovium of patients with RA. It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1.1 regulates RA-FLS adhesion through controlling the plasma membrane expression and activat...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Tanner, M. R., Pennington, M. W., Laragione, T., Gulko, P. S., Beeton, C. Tags: Research Source Type: research
Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples [Research]
This study aimed to characterize the effects of varying input RNA integrity [estimated as RNA integrity number (RIN)] on transcript level estimates and delineate the characteristic differences between transcripts that differ in degradation rate. The study used ribodepleted total RNA sequencing data from a real-life clinically collected set (n = 32) of human solid tissue (placenta) samples. RIN-dependent alterations in gene expression profiles were quantified by using DESeq2 software. Our results indicate that small differences in RNA integrity affect gene expression quantification by introducing a moderate and pervasive bi...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Reiman, M., Laan, M., Rull, K., Sober, S. Tags: Research Source Type: research
Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture [Research]
In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.—Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture. (Source: FASEB Journal)
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Hojlund, K., Thoren, P., Stener-Victorin, E. Tags: Research Source Type: research
A TSPO ligand attenuates brain injury after intracerebral hemorrhage [Research]
In this study, we determined the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In collagenase-induced ICH mice, the protection of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α. Etifoxine improved blood&nd...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Li, M., Ren, H., Sheth, K. N., Shi, F.-D., Liu, Q. Tags: Research Source Type: research
The role of CB1 in intestinal permeability and inflammation [Research]
The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL1...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., OSullivan, S. E. Tags: Research Source Type: research
TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin [Research]
We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morpholo...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregon, A., Raghunath, M. Tags: Research Source Type: research
Avian blastoderm dormancy arrests cells in G2 and suppresses apoptosis [Research]
In most avian species, the early embryo suspends development when the ambient temperature is too low; the resultant dormant state is called cold torpor. However, very little is known about dormant avian embryos at the cellular level. To investigate the molecular processes that occur in the chicken blastoderm during cold torpor, we performed transcriptome analysis and investigated cellular responses in dormant embryos. In embryos stored at low temperature, we observed up-regulation of genes and proteins related to endoplasmic reticulum stress and stress-activated protein kinase signaling. In addition, the proportion of earl...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Ko, M. H., Hwang, Y. S., Rim, J. S., Han, H. J., Han, J. Y. Tags: Research Source Type: research
Modulation of innate immunity of patients with Alzheimers disease by omega-3 fatty acids [Review]
The innate immune system of patients with Alzheimer’s disease and mild cognitive impairment (MCI) is deregulated with highly increased or decreased transcription of inflammatory genes and consistently depressed phagocytosis of amyloid-β1-42 (Aβ) by monocytes and macrophages. Current immune therapies target single mechanisms in the adaptive immune system but not innate immunity. Here, we summarize recent advances in therapy by -3, -6, and epoxy fatty acids; specialized proresolving mediators; and vitamin D3 that have proven immune effects and emerging cognitive effects in patients with MCI. The hypothesis of...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Fiala, M., Kooij, G., Wagner, K., Hammock, B., Pellegrini, M. Tags: Review Source Type: research
Synthetic: How Life Got Made: by Sylvia Roosth * University of Chicago Press, Chicago, 2017 [Book Review]
(Source: FASEB Journal)
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Maienschein, J. Tags: Book Review Source Type: research
Herpes simplex virus type 1 and Alzheimers disease: possible mechanisms and signposts [Alzheimer's Disease Review Series]
Support for the concept that herpes simplex virus type 1 (HSV1), when present in the brains of apolipoprotein E-4 carriers, is a major risk for Alzheimer’s disease (AD) is increasing steadily, with over 120 publications providing direct or indirect evidence relevant to the hypothesis. No articles have contested the concept, apart from 3 published 13–18 yr ago. This review describes very recent studies on the role of HSV1 but refers also to older studies that provide background for some lesser-known related topics not covered in other recent reviews; these include the relevance of herpes simplex encephalitis and...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Itzhaki, R. F. Tags: Alzheimer ' s Disease Review Series Source Type: research
Categorizing biomedical research: the basics of translation [Perspective]
As biomedical research has evolved over the past century, the terminology employed to categorize it has failed to evolve in parallel to accommodate the implications of these changes. In particular, the terms basic research and translational research as used today in biomedicine seem especially problematic. Here we review the origins of these terms, analyze some of the conceptual confusions attendant to their current use, and assess some of the deleterious consequences of these confusions. We summarize that the distinction between basic and translational biomedical research is an anachronism. Elimination of this often conte...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Flier, J. S., Loscalzo, J. Tags: Perspective Source Type: research
