Publications by authors named "Sellak H"

Children with beta-thalassemia (BT) present with an increase in carotid intima-medial thickness, an early sign suggestive of premature atherosclerosis. However, it is unknown if there is a direct relationship between BT and atherosclerotic disease. To evaluate this, wild-type (WT, littermates) and BT (Hbb) mice, both male and female, were placed on a 3-mo high-fat diet with low-density lipoprotein receptor suppression via overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation (D377Y).

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The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3-fold increase in intestinal permeability as assessed via FITC-dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice ( = 4,  < 0.

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Precision health seeks to optimise behavioural interventions by delivering personalised support to those in need, when and where they need it. Conceptualised a decade ago, progress toward this vision of personally relevant and effective population-wide interventions continues to evolve. This scoping review aimed to map the state of precision health behaviour change intervention research.

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Article Synopsis
  • Sickle cell disease (SCD) leads to frequent vascular issues and poor organ performance, with impaired blood flow recovery following vascular injury.
  • Research was conducted on SCD mice to see if boosting nitric oxide levels could enhance recovery after induced vascular damage.
  • The results showed that treatments like L-Arginine and NO-generating hydrogels did not help recovery and might even worsen the situation by increasing oxidative stress in SCD mice.
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Objective: To determine progress and gaps in global precision health research, examining whether precision health studies integrate multiple types of information for health promotion or restoration.

Design: Scoping review.

Data Sources: Searches in Medline (OVID), PsycINFO (OVID), Embase, Scopus, Web of Science and grey literature (Google Scholar) were carried out in June 2020.

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Background: The COVID-19 pandemic has had enormous impacts on people's lives, including disruptions to their normal ways of behaving, working, and interacting with others. Understanding and documenting these experiences is important to inform the ongoing response to COVID-19 and disaster preparedness efforts.

Objective: The aim of this study was to examine the psychosocial impacts of COVID-19 on a sample of Australian adults.

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Article Synopsis
  • Precision health is an emerging research field that needs clearer definitions and differentiation from precision medicine to effectively address global health challenges.
  • A scoping review will analyze the last decade of human precision health research to identify similarities, discrepancies, and research gaps in the literature.
  • Results will be shared through professional networks, conferences, and scientific journal publications.
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Healthcare and wellness support that consider context within different dimensions can lead to intelligent, personalised recommendations that will more likely be accepted and acted upon by consumers. In this paper, we look at the main components of traditional personalised healthcare and wellness support services, and identify some of the challenges that should be addressed in creating a more intelligent and efficient solution. Our contribution lies in defining away forward in terms of designing such a solution.

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Background: The mechanisms that regulate fetal hemoglobin (HbF) expression in sickle cell disease (SCD) remain elusive. We previously showed that steady-state SCD patients with high HbF levels due to a gene mutation demonstrate strong inverse correlations between HbF levels and leukocyte counts, suggesting that leukocytes play a role in regulating HbF in SCD.

Materials And Methods: To further investigate the role of leukocytes in HbF expression in SCD, we examined the presence of HbF silencing factors in the serum of 82 SCD patients who received hydroxyurea (HU) therapy.

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Much attention has been directed to the physiological effects of nitric oxide (NO)-cGMP signaling, but virtually nothing is known about its hematologic effects. We reported for the first time that cGMP signaling induces human γ-globin gene expression. Aiming at developing novel therapeutics for anemia, we examined here the hematologic effects of NO-cGMP signaling in vivo and in vitro.

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Retinal hyperpermeability and subsequent macular edema is a cardinal feature of early diabetic retinopathy (DR). Here, we investigated the role of bioactive lipid metabolites, in particular 12/15-lipoxygenase (LOX)-derived metabolites, in this process. LC/MS lipidomic screen of human retinal endothelial cells (HRECs) demonstrated that 15-HETE was the only significantly increased metabolite (2.

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The low-voltage-activated T-type Ca(2+) channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood.

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The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an important role in many cardiovascular diseases. In the last two decades, in vitro and in vivo models of vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP, cytokine, and growth factor stimulation.

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The transcriptional activator β-catenin is a key mediator of the canonical Wnt signaling pathway. β-catenin itself does not bind DNA but functions via interaction with T-cell factor (TCF)/lymphoid-enhancing factor (LEF) transcription factors. Thus, in the case of active Wnt signaling, β-catenin, in cooperation with TCF/LEF proteins family, activates the expression of a wide variety of genes.

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Article Synopsis
  • The study investigates how the 3'-untranslated region (3'UTR) of PKG-I mRNA controls the expression of PKG-I in vascular smooth muscle cells (VSMCs).
  • Researchers found that a specific 1.2-kb 3'UTR of PKG-I had the highest activity during experiments, indicating its important role in stabilizing mRNA expression.
  • The presence of AU-rich regions in the 3'UTR was shown to interact with specific proteins, suggesting that PKG-I expression is regulated post-transcriptionally in VSMCs.
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Although the regulation of smooth muscle cell (SMC) gene expression by cGMP-dependent protein kinase (PKG) is now recognized, the mechanisms underlying these effects are not fully understood. In this study, we report that PKG-I stimulates myocardin/serum response factor (SRF)-dependent gene expression in vascular SMCs. The expression of PKG in PKG-deficient cells enhanced myocardin-induced SM22 promoter activity in a concentration-dependent fashion.

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Regulated P-selectin surface expression provides a rapid measure for endothelial transition to a proinflammatory phenotype. In general, P-selectin surface expression results from Weibel-Palade body (WPb) exocytosis. Yet, it is unclear whether pulmonary capillary endothelium possesses WPbs or regulated P-selectin surface expression and, if so, how inflammatory stimuli initiate exocytosis.

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The T-type Ca2+ channel Cav3.1 subunit is present in pulmonary microvascular endothelial cells (PMVECs), but not in pulmonary artery endothelial cells (PAECs). The present study sought to assess the role of Cav3.

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This basic science review examines the role of cGMP and cGMP-dependent protein kinase (PKG) in the regulation of vascular smooth muscle cell (VSMC) phenotype. The first such studies suggested a role for nitric oxide (NO) and atrial natriuretic peptides (ANP), and the downstream second messenger cGMP, in the inhibition of VSMC proliferation. Subsequently, many laboratories confirmed the anti-proliferative effects of the cGMP pathway in cultured cells and the anti-atherosclerotic effects of the pathway in in vivo animal models.

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Cyclic GMP-dependent protein kinase I plays a pivotal role in regulating smooth muscle cell relaxation, growth, and differentiation. Expression of the enzyme varies greatly in smooth muscle and in other tissues and cell types, yet little is known regarding the mechanisms regulating cGMP-dependent protein kinase gene expression. The present work was undertaken to characterize the mechanisms controlling kinase gene expression in vascular smooth muscle cells.

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NO and cGMP have antigrowth and anti-inflammatory effects on the vessel wall in response to injury. It is well established that after vascular injury proinflammatory cytokines are involved in vascular wall remodeling. The purpose of this study was to ascertain the signaling mechanisms involved in cGMP-dependent protein kinase (PKG) suppression by inflammatory cytokines in primary bovine aortic vascular smooth muscle cells (VSMC).

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cGMP-dependent protein kinase (PKG) expression is highly variable and decreases in cultured vascular smooth muscle cells (VSMCs), exposure of cells to nitric oxide (NO), or in response to balloon catheter injury in vivo. In this study, the mechanisms of human type I PKG-alpha (PKG-Ialpha) gene expression were examined. Three structurally unrelated NO donors decreased PKG-Ialpha promoter activity after transfection of a promoter/luciferase construct in VSMCs.

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cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell.

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Excessive or premature contractions of uterine smooth muscle may contribute to preterm labor. Contractile stimuli induce myosin and actin filament interactions through calcium-dependent myosin phosphorylation. The mechanisms that maintain myometrial quiescence until term are not well established, but may include control of calcium levels by nitric oxide and cGMP signaling and thin filament (caldesmon and calponin) regulation.

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Contractility of uterine smooth muscle is essential for the cyclic shedding of the endometrial lining and also for expulsion of the fetus during parturition. The nitric oxide (NO)-cGMP signaling pathway is involved in smooth muscle relaxation. The downstream target of this pathway essential for decreasing cytoplasmic calcium and muscle tone is the cGMP-dependent protein kinase (PKG).

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