Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β.

Metabolic dysregulation in fibroblasts is implicated in the profibrotic actions of transforming growth factor-β (TGF-β). Here, we present evidence that hexokinase 2 (HK2) is important for mediating the fibroproliferative activity of TGF-β both in vitro and in vivo. Both Smad-dependent and Smad-independent TGF-β signaling induced HK2 accumulation in murine and human lung fibroblasts through induction of the transcription factor c-Myc.

Fatty acid synthase is required for profibrotic TGF-β signaling.

Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-β-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1.

Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling.

TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3).

Profibrotic up-regulation of glucose transporter 1 by TGF-β involves activation of MEK and mammalian target of rapamycin complex 2 pathways.

TGF-β plays a central role in the pathogenesis of fibroproliferative disorders. Defining the exact underlying molecular basis is therefore critical for the development of viable therapeutic strategies. Here, we show that expression of the facilitative glucose transporter 1 (GLUT1) is induced by TGF-β in fibroblast lines and primary cells and is required for the profibrotic effects of TGF-β.

The role of exercise in fall prevention for older adults.

This article reviews the evidence for the effectiveness of stand-alone exercise interventions and multifactorial intervention strategies that include exercise in lowering fall incidence rates and/or fall risk among older adults residing in the community, acute, subacute, and long-term care settings. Stand-alone exercise programs that emphasize multiple exercise categories are effective in reducing fall rates and fall risk in community-residing older adults, and may also be effective when conducted for a sufficient duration with older adult patients in subacute settings. In contrast, multifactorial fall risk reduction programs that include exercise as a component and are delivered by a multidisciplinary team are more effective in lowering fall rates in long-term care settings.

Cardiovascular response to interpersonal provocation and mental arithmetic among high and low hostile young adult males.

To examine the relation between hostility and cardiovascular reactivity to stress, 42 undergraduate men were categorized into high and low hostile groups based on responses to the Cook Medley Hostility Scale. Participants engaged in two laboratory tasks: a Cognitive Task (mental arithmetic) and a Social Task (confrontation role-play). Cardiovascular measures of heart rate and blood pressure were obtained throughout rest and task periods and participants provided ratings of state anger and forgiveness following task completion.

Predicting which older adults will or will not fall using the Fullerton Advanced Balance scale.

Objective: The purpose of this study was to determine if the Fullerton Advanced Balance (FAB) scale can predict faller status in a group of independently functioning older adults.

Design: A cross-sectional design was used to establish the sensitivity and specificity of the FAB scale to predict faller status based on a retrospective self-reported fall history. For the purpose of this study, a faller was classified as an older adult with a history of 2 or more falls in the previous 12 months.