Panagiotis Liakos

University of Thessaly | UTH · Laboratory of Biochemistry (Sector of Basic Science)

Background: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444...

Background: Multiple Sclerosis (MS) is the most common autoimmune disease of the central nervous system. Up to this day, no single accurate prognostic biomarker has been established in this disease. Neurofilaments are neuronal scaffold proteins upon axonal damage and have gained attention as potential biomarkers in MS. Methods: Neurofilament light-...

PurposeThe sleep clinical record (SCR) has been used to diagnose obstructive sleep apnea syndrome (OSAS) in children when access to polysomnography (PSG) is limited. Our aim was to determine the best SCR score that could facilitate diagnosis of moderate-to-severe OSAS in children with snoring.Methods Healthy children with history of snoring, who we...

The genetic basis of migraine is rather complex. The rs2651899 in the PR/SET domain 16 (PRDM16) gene, the rs10166942 near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene, and the rs11172113 in the LDL receptor-related protein 1 (LRP1) gene, have been associated with migraine in a genome-wide association study (GWAS...

The predominance of cardiovascular diseases among men compared to premenopausal women has been attributed to testosterone, which is implicated in vascular remodeling. Molecular mechanisms underlying its role have not been clarified but oxidative stress‐induced inflammation may be important. We therefore investigated in vitro the effects of testoste...

Calcidiol (25 hydroxy vitamin D3) is the major circulating metabolite of vitamin D in the human body and direct precursor of calcitriol (1,25 dihydroxy vitamin D3) with generally known hormonal activity. The biological activities of calcidiol have not been widely investigated despite its high structural similarity with calcitriol and hundreds of...

Background and Objectives: To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods: A case-control study was performed. Patients with definite sporadic ALS were prospectively and conse...

Objective High serum erythropoietin (EPO) levels have been reported in adult patients with obstructive sleep apnea (OSA), however there is a lack of related literature in children with OSA. The main objective of this study was to explore the potential use of EPO as a pediatric OSA biomarker by exploring the relationship between serum EPO levels and...

BACKGROUND The rs616147 polymorphism of the myelin-associated oligodendrocyte basic protein (MOBP) gene locus has been associated with amyotrophic lateral sclerosis (ALS). ALS and Parkinson's disease (PD) are two common neurodegenerative disorders that share features regarding their etiology, pathophysiology, and genetic backgrounds. While the MOBP...

Hypoxia-inducible factor 2 (HIF-2), is essential for cellular response to hypoxia and holds an important role in erythropoiesis, angiogenesis, tissue invasion and metastasis, thus, constituting an important therapeutic target. Maximal HIF-2 transcriptional activation requires HIF-2α phosphorylation by ERK1/2 that impairs its CRM1-mediated nuclear e...

BACKGROUND Alzheimer’s (AD) and Parkinson’s diseases (PD) share a few elements of their clinical, pathological and genetic backgrounds. The CD33 rs3865444 has emerged as a strong genetic locus associated with AD through genome-wide association study (GWAS). However, little is known for its role in PD. OBJECTIVE To assess the role of CD33 rs3865444...

Background: Parkinson’s disease (PD) is the second commonest neurodegenerative disease. The genetic basis of PD is indisputable. Both ADORA2A rs5760423 and CYP1A2 rs762551 have been linked to PD, to some extent, but the exact role of those polymorphisms in PD remains controversial. Objective: We assessed the role of ADORA2A rs5760423 and CYP1A2 rs7...

Background: Parkinson's disease (PD) is the second commonest neurodegenerative disease. The genetic basis of PD is indisputable. Both ADORA2A rs5760423 and CYP1A2 rs762551 have been linked to PD, to some extent, but the exact role of those polymorphisms in PD remains controversial. Objective: We assessed the role of ADORA2A rs5760423 and CYP1A2...

Hypoxia-inducible transcription factors 1 and 2 (HIFs) are major mediators of cancer development and progression and validated targets for cancer therapy. Although calcitriol, the biologically active metabolite of vitamin D, was attributed with anticancer properties, there is little information on the effect of calcitriol on HIFs and the mechanism...

Background Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates i...

Purpose: Growth factors such as fibroblast growth factor 2 (FGF-2) and hepatocyte growth factor (HGF) appear at high levels in prostate cancer (PC). Abiraterone is an androgen biosynthesis inhibitor which is currently in use as a standard treatment in clinics to impair tumor growth. Development of resistance to anticancer therapies is unfortunatel...

Background This study was conducted to investigate whether high-tidal-volume mechanical ventilation is associated with increased lung inflammation compared with low-tidal-volume mechanical ventilation in critically ill patients with no evidence of lung injury. Methods In this prospective, single-blind, randomized (1:1), parallel-group study, 18 cr...

Background: Remote ischemic preconditioning (RIPC) has been shown to reduce myocardial ischemiareperfusion injury. However, its efficacy in preventing postoperative atrial fibrillation (POAF) remains unsettled. Methods: A total of 97 eligible patients were prospectively randomized to receive either RIPC or shamRIPC (control) prior to coronary arter...

Corticotropin‐releasing hormone, which is the predominant regulator of neuroendocrine responses to stress, attenuates inflammation through stimulation of glucocorticoid release. Enhanced corticotropin‐releasing hormone expression has been detected in inflammatory cells of the vascular endothelium, where it acts as a local regulator of endothelial r...

Hypoxia-inducible factor 2 (HIF-2) is a principal component of the cellular response to oxygen deprivation (hypoxia). Its inducible subunit, HIF-2α (also known as EPAS1), is controlled by oxygen-dependent as well as oxygen-independent mechanisms, such as phosphorylation. We show here that HIF-2α is phosphorylated under hypoxia (1% O2) by extracellu...

Purpose: The standard treatment of rectal cancer is surgery along with preoperative radiotherapy, administered alone or in combination with chemotherapy. Preoperative chemoradiotherapy (preCRT) is widely used as it allows better local control and the use of sphincter-saving surgery. Pathological response after preCRT has been shown to be a signifi...

Abstract BACKGROUND: The use of surgical meshes in ventral hernia repair has significantly reduced hernia recurrence rates. However, when placed intraperitoneally prosthetic materials can trigger the development of peritoneal adhesions. The present experimental study evaluated the combined icodextrin 4% and dimetindene maleate treatment in preventi...

Low oxygen tension exerts a profound effect on the replication of several DNA and RNA viruses. In vitro propagation of Dengue virus (DENV) has been conventionally studied under atmospheric oxygen levels despite that in vivo, the tissue microenvironment is hypoxic. Here, we compared the efficiency of DENV replication in liver cells, monocytes, and e...

Objectives: In children with snoring, increased production of leukotriene B4 (LTB4) may promote tonsillar hypertrophy and sleep-disordered breathing (SDB) or conversely SDB may enhance LTB4 synthesis. We explored whether: i) high LTB4 serum levels predict tonsillar hypertrophy; and ii) SDB severity correlates with LTB4 serum concentration. Method...

Angiogenesis is a key enabling feature of mammalian embryonic development and tumor progression, which provides oxygen and nutrients that are required for vessel growth and tumor cell growth, respectively. Hypoxia is a driver of this phenomenon and is considered to be one of the most potent initiators of angiogenesis both in vitro and in vivo throu...

Tissue hypoxia affects gene expression through the hypoxia-inducible transcription factors, HIF-1 and HIF-2, in both physiological and pathological angiogenesis. Angiogenesis is a complex response of endothelial cells integrating cell proliferation, migration, tube formation and their interaction with the extracellular matrix through integrin recep...

PurposeBortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. MethodsNCI-H929 and RPMI-8226 (human MM cell lines) were...

Hypoxia Inducible Factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2α, involves post-translational modifications. Here, we demonstrate that casein kinase 1δ (CK1δ) phosphorylates HIF-2α at Ser383 and Thr528 in vitro Disruption of these phosphorylation sites and...

Aims: In a previous study, children with obstructive sleep-disordered breathing (SDB) had higher leukotriene B4 (LTB4) serum levels than control subjects and apnea-hypopnea index (AHI) was a significant predictor of these levels (Shen 2014). Furthermore, LTB4 and enzymes for its biosynthesis were detected in hypertrophic tonsillar tissue from child...

e16083 Background: In the prostatic epithelium endothelin-1 (ET-1), fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell proliferation and inhibition of apoptosis. The aim of this study is to investigate whether neuropeptides such as ET-1 and growth factors such as FGF and HGF may constitute an alternate pathway...

Development of drug resistance after standard chemotherapy for glioblastoma multiforme (GBM) with temozolomide (TMZ) is associated with poor prognosis of GBM patients and is at least partially mediated by a direct DNA repair pathway involving O6-methylguanine methyltransferase (MGMT). This enzyme is under post-translational control by a multisubuni...

Hypoxia Inducible Factor-1 (HIF-1), a dimeric transcription factor of the bHLH-PAS family, is comprised of HIF-1α, which is inducible by hypoxia and ARNT or HIF-1β, which is constitutively expressed. HIF-1 is involved in cellular homeostasis under hypoxia, in development and in several diseases affected by oxygen availability, particularly cancer....

Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of the hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV pro...

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smoke...

Bovine zona glomerulosa cells, on the first day of culture, produce aldosterone as their major steroid with no detectable cortisol secretion. Continuous incubation with ACTH had no effect on aldosterone production nor on aldosterone synthase activity. This treatment resulted in a dose and time dependent rise in 17α-hydroxylase activity, in parallel...

Adaptation to hypoxia involves hypoxia-inducible transcription factors (HIFs) and requires reprogramming of cellular metabolism that is essential during both physiological and pathological processes. In contrast to the established role of HIF-1 in glucose metabolism, the involvement of HIFs and the molecular mechanisms concerning the effects of hyp...

Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasom...

Bortezomib represents the first proteasome inhibitor (PI) with demonstrated antitumor activity in the clinical setting, particularly for treatment of hematological malignancies. At the preclinical level, its action is shown to be mediated by induction of growth arrest and apoptosis in many tumor types, including androgen-dependent (AD) and androgen...

Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative stress and inflammation in the airway. The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhal...

Local or 'Immune' Corticotropin-Releasing Hormone (CRH) is secreted in peripheral tissues and plays a direct immunomodulatory role as an endocrine or paracrine mediator of inflammation. The present study was undertaken to determine whether CRH affects the endothelial redox state. Accordingly, intracellular reactive oxygen species (ROS) content and...

Nitric oxide (NO) is considered as an intracellular messenger in the brain. Its involvement in learning and memory processes has been proposed. The present study was designed to investigate the effects of the NO-releasing derivative of ferulic acid NCX 2057 on rats' recognition memory. For this purpose the object recognition task was selected. Post...

Diminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB). To assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure. Morning nitri...

Pharmacological induction of fetal hemoglobin (HbF) is beneficial for some patients with β-thalassemia and also ameliorates the severity of pain episodes in sickle cell anemia, mainly by hydroxyurea (HU). However, refractoriness or poor response of some patients treated with HU triggered research for other drugs. In the present study, we evaluated...

Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-ind...

Quercetin, a flavonoid with anti-oxidant, metal chelating, kinase modulating and anti-proliferative properties, can induce hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia, but its mechanism of action has not been determined. In this study we characterized the induction of HIF-1alpha and the inhibition of cell proliferation caused by querce...

Apolipoprotein E (ApoE), and especially its epsilon4 isoform, is considered a risk factor predisposing to coronary heart disease. We hypothesized that the absence of epsilon4 allele offers a better chance for longer life. So we compared the prevalence of ApoE genotypes in 80 healthy aged individuals (HAI) (>80 years) and 391 Greek adults (median ag...

Pharmacological induction of fetal hemoglobin (HbF) is beneficial for some patients with β-thalassemia and also ameliorates the severity of pain episodes in sickle cell anemia, mainly by hydroxyurea (HU). However, refractoriness or poor response of some patients treated with HU triggered research for other drugs. In the present study, we evaluated...

The iron-chelator desferrioxamine (DFO) and the transition metal cobalt induce hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. DFO stabilizes HIF-1alpha from proteolysis by inhibiting the activity of iron-dependent prolyl hydroxylases, but the mechanism of action of cobalt is not fully elucidated. The purpose of this study was to examine...

The present study attempts to shed light on the role and the relative position of the Na(+)/H(+) exchanger isoform 1 (NHE1) and the extracellular signal-regulated kinase (ERK) in HEp-2 cell signaling pathways concerning a diverse range of cellular functions such as regulation of intracellular pH (pHi), DNA synthesis, production of reactive oxygen s...

The aim of the present study was to evaluate the effect of latanoprost monotherapy on the aqueous humour concentrations of TGF-beta1, MMP-2, TIMP-2, MMP-9 and gelatinolytic activity in patients treated for exfoliative glaucoma (XFG). Aqueous samples from 50 XFG patients treated with latanoprost and 50 age-matched XFG patients treated with timolol w...

This study aims to demonstrate the effect of high glucose concentrations on NHE-1 and PK activities and investigate the implicated signal transduction pathways. Erythrocytes drawn from healthy volunteers were incubated in the presence of 5 or 50 mM of glucose, fructose, galactose or mannitol. When appropriate, specific inhibitors of NHE-1, PKC or p...

Transforming growth factor beta1 (TGFbeta1) has been shown to exert strong inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular targets of TGFbeta1 in adrenocortical cells appear to differ between species. Here, we report the first characterization of the regulatory effects of TGFbeta1 on the steroidogenic functions of...

We present an in vivo and in vitro study of congenital adrenal hyperplasia in a patient with 11beta-hydroxylase deficiency. Sequencing of the CYP11B1 gene showed two new base substitutions, a conservative 954 G-->C transversion at the last base of exon 5 (T318T), and a IVS8 + 4A-->G transition in intron 8. In addition, two polymorphisms were found...

Endothelial cells lining vessels of endocrine tissues are fenestrated. Interactions with the local environment via either soluble factors or cell–cell interactions appear to govern this terminal endothelial differentiation. Adrenocorticotropin (ACTH) has previously been reported to modulate endothelial fenestration in the rat adrenal cortex. Since...

Endothelial cells lining vessels of endocrine tissues are fenestrated. Interactions with the local environment via either soluble factors or cell–cell interactions appear to govern this terminal endothelial differentiation. Adrenocorticotropin (ACTH) has previously been reported to modulate endothelial fenestration in the rat adrenal cortex. Since...

Among the five members of the melanocortin receptor (MC-R) family, MC2 and MC5 are expressed in peripheral tissues. The receptor MC2 (ACTH receptor) almost exclusively expressed in the adrenal cortex whereas MC5-R is expressed in several organs including the adrenal cortex. Both receptors bind ACTH and activate adenylate cyclase. The aim of this wo...

We studied a patient with food-induced, ACTH-independent, Cushing's syndrome and a unilateral adrenocortical adenoma. In vivo cortisol secretion was stimulated by mixed, glucidic, lipidic, or proteic meals. Plasma ACTH levels were undetectable, but iv injection of ACTH stimulated cortisol secretion. Unilateral adrenalectomy was followed by hypocort...

The recent cloning of a family of melanocortin receptors (MC-R) has identified five distinct G protein- and adenylate cyclase-coupled receptors. The MC2-receptor (MC2-R) preferentially binds ACTH. It is expressed in the adrenal cortex and is hence considered to be the ACTH receptor. The MC5-receptor (MC5-R) binds ACTH and alpha-MSH and is more wide...

We studied in vitro an adrenal tumor responsible for food-dependent, ACTH independent, Cushing's's syndrome. Cortisol secretion by isolated tumor cells was stimulated by GIP and ACTH, but not by the gut hormone glucagon-like peptide-1 (GLP-1). Both GIP and ACTH stimulated production of cAMP but not inositol 1,4,5-trisphosphate IP3). In quiescent tu...

Angiotensin II (ANG II) has long been known for its pressor and growth-promoting effects, which are both mediated by the AT1 receptor. By contrast, the AT2 receptor has recently been reported to mediate inhibition of proliferation through as yet undefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not...

Bovine zona glomerulosa cells, on the first day of culture, produce aldosterone as their major steroid with no detectable cortisol secretion. Continuous incubation with ACTH had no effect on aldosterone production nor on aldosterone synthase activity. This treatment resulted in a dose and time dependent rise in 17 alpha-hydroxylase activity, in par...