kyriaki hat

Στην παρούσα μελέτη: α) Διερευνήθηκε η δραστικότητα της γεφιτινίμπης σε κυτταρικές σειρές γλοιοβλαστώματος (Α172) και νευροβλαστώματος (SH-SY5Y, BE(2)M17) και η συσχέτιση της συγκέντρωσής της με την αναστολή του κυτταρικού πολλαπλασιασμού και της φωσφορυλίωσης στην τυροσινική κινάση του υποδοχέα του επιδερμιδικού αυξητικού παράγοντα EGFR (Epidermal Growth Factor Receptor). β) Πραγματοποιήθηκε μικροεγκλεισμός της γεφιτινίμπης σε β-κυκλοδεξτρίνες (CyDs) (DIMEB/TRIMEB, 2-υδροξυ-προπυλιωμένη-β-CyD) για βελτίωση της υδατοδιαλυτότητάς της. γ) Μελετήθηκαν οι φυσικοχημικές ιδιότητες των προϊόντων εγκλεισμού και η δραστικότητά τους σε κύτταρα νευροβλαστώματος. Ο κυτταρικός πολλαπλασιασμός, παρουσία διαφόρων συγκεντρώσεων γεφιτινίμπης, CyDs και προϊόντων εγκλεισμού εκτιμήθηκε με τη χρωματομετρική μέθοδο κυανούν alamar. Η φωσφορυλίωση του καταλοίπου τυροσίνης Tyr 1068 του EGFR εκτιμήθηκε με την ανοσοενζυμική μέθοδο ELISA και τα επίπεδα έκφρασης του EGFR στα κύτταρα με ανοσοϊστοχημεία. Με τη φασματοσκοπία NMR αναδείξαμε τον τρόπο εγκλεισμού της γεφιτινίμπης στις CyDs. Με προσομοιώσεις μοριακής δυναμικής αναπαραστήσαμε την τρισδιάστατη μοριακή δομή και μιμηθήκαμε τη συμπεριφορά των προϊόντων εγκλεισμού. Η σειρά SH-SY5Y εκφράζει υψηλότερα επίπεδα EGFR. Στην ELISA παρατηρήθηκε μείωση της φωσφορυλίωσης της τυροσίνης 1068 του EGFR, καθώς αυξανόταν η συγκέντρωση της γεφιτινίμπης, ενώ τα επίπεδα του EGFR δεν επηρεάζονταν. Στη δοκιμασία κυανούν alamar, καθώς αυξανόταν η συγκέντρωση της γεφιτινίμπης και των συμπλόκων εγκλεισμού και ο χρόνος έκθεσης των κυττάρων στα φάρμακα παρατηρήθηκε ελάττωση της κυτταρικής βιωσιμότητας, ιδίως σε έκθεση στο γεφιτινίμπη/2-υδροξυ-προπυλιωμένη-β-CyD. Αντίθετα, η έκθεση των κυττάρων σε αυξανόμενες συγκεντρώσεις κυκλοδεξτρινών δεν είχε επίδραση στα κύτταρα, με εξαίρεση τις υψηλότερες συγκεντρώσεις. Με φασματοσκοπία NMR επιβεβαιώσαμε το σχηματισμό προϊόντων εγκλεισμού της γεφιτινίμπης με τις β-CyDs σε υδατικό διάλυμα και την αύξηση της διαλυτότητάς της, μετά τον εγκλεισμό, καθώς είναι πλήρως αδιάλυτη σε νερό. Παρουσία των DIMEB, TRIMEB και 2-υδροξυ-προπυλιωμένης-β-CyD η διαλυτότητά της αυξήθηκε σε ~1,5 mM, ~1,8 mM και 0,2 mM, αντίστοιχα. Στα πειράματα μοριακής δυναμικής η ενέργεια της καλύτερης διαμόρφωσης των συμπλόκων εγκλεισμού υπολογίσθηκε ΔG0=-4, 6kcal/mol, -4,2kcal/mol και -4,6kcal/mol στα γεφιτινίμπη/DΙMEB, γεφιτινίμπη /TRIMEB και γεφιτινίμπη/2-υδροξυ-προπυλιωμένη-β-CyD, αντίστοιχα. Αποδείξαμε ότι η γεφιτινίμπη και τα προϊόντα εγκλεισμού της έχουν κυτταροτοξική δράση σε κυτταρικές σειρές νευροβλαστώματος και γλοιοβλαστώματος. Τα προϊόντα εγκλεισμού είχαν υψηλότερη κυτταροτοξική δράση, ιδίως το γεφιτινίμπη/2-υδροξυ-προπυλιωμένη-β-CyD. Η αναστολή του κυτταρικού πολλαπλασιασμού συνέπιπτε με αναστολή της φωσφορυλίωσης στην τυροσίνη 1068. Η βελτίωση της διαλυτότητας της γεφιτινίμπης οφείλονταν σε απομάκρυνση από το υδατικό διάλυμα του υδρόφοβου τμήματος του φαρμάκου, καθώς εγκλείεται στην κοιλότητα της CyD. Τα συμπεράσματα της παρούσας μελέτης αποτελούν τη βάση έρευνας για τη χρήση αναστολέων τυροσινικής κινάσης στην αντιμετώπιση του νευροβλαστώματος και τη στροφή σε στοχευμένες θεραπείες με υψηλότερη αποτελεσματικότητα και λιγότερες παρενέργειες.

The present study identifies the phytochemical profile of a hydroalcoholic extract derived from Smilax aspera leaves and stems, estimates its antioxidant capacity and evaluates its cytotoxic activity against glioblastoma (A172 cell line) and rhabdomyosarcoma (TE671 cell line). Chemical analysis of leaves and stems was performed with liquid chromatography analysis combined with a quadrupole time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The antioxidant activity of the extract was evaluated with the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the 2,2′-azinobis[3-ethylbenzthiazoline-6-acid)] (ABTS) assays. Cell viability was examined using the alamar blue assay. Most of the compounds tentatively identified belonged to the flavonoids family, with rutin being the most abundant, followed by luteolin. The extract showed potent antioxidant activity which corresponded to 13.9 ± 1.91 μg/mL (DPPH assay) and 6.27 ± 1.7 μg/mL (ABTS assay), expressed as IC50 values. The extract in...

Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. However, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methylated β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-CD) was determined by X-ray crystallography. The structural investigation was complemented by molecular dynamics simulations. The cytotoxicity of CBD and its complexes with RM-β-CD and HP-β-CD was tested on two cell lines, the A172 glioblas...

Rosmarinus officinalis is a well-studied plant, known for its therapeutic properties. However, its biological activity against several diseases is not known in detail. The aim of this study is to present new data regarding the cytotoxic activity of a hydroethanolic extract of Rosmarinus officinalis on glioblastoma (A172) and rhabdomyosarcoma (TE671) cancer cell lines. The chemical composition of the extract is evaluated using liquid chromatography combined with time-of-flight mass spectrometry, alongside its total phenolic content and antioxidant activity. The extract showed a promising time- and dose-dependent cytotoxic activity against both cell lines. The lowest IC50 values for both cell lines were calculated at 72 h after treatment and correspond to 0.249 ± 1.09 mg/mL for TE671 cell line and 0.577 ± 0.98 mg/mL for A172 cell line. The extract presented high phenolic content, equal to 35.65 ± 0.03 mg GAE/g of dry material as well as a strong antioxidant activity. The IC50 values f...

As a consequence of the progress of the global vaccination against the COVID-19 disease, fast, accurate and affordable assays are needed for monitoring the efficiency of developing immunity against the coronavirus at the population level. In this context, we herewith report the proof-of-concept development of an innovative bioelectric biosensor for the ultra-detection (in less than three minutes) of IgG antibodies against the SARS-CoV-2 S1 spike antigen. The biosensor comprises a disposable set of screen-printed electrodes upon which are immobilized cells engineered to bear the S1 protein on their surface. When anti-S1 antibodies are presented to the engineered cell population, a rapid, specific, and selective change of the cell membrane potential occurs; this is in turn recorded by a bespoke portable potentiometer. End results are communicated via Bluetooth to a smartphone equipped with a customized user interface. By using the novel biosensor, anti-S1 antibodies could be detected ...

Crocus sativus L. has various pharmacological properties, known for over 3600 years. These properties are attributed mainly to biologically active substances, which belong to the terpenoid group and include crocins, picrocrocin and safranal. The aim of the current work was to examine the effects of crocins (CRCs) and their methyl ester derivate dimethylcrocetin (DMCRT) on glioblastoma and rhabdomyosarcoma cell lines, in terms of cytotoxicity and gene expression, implicated in proapoptotic and cell survival pathways. Cell cytotoxicity was assessed with Alamar Blue fluorescence assay after treatment with saffron carotenoids for 24, 48 and 72 h and concentrations ranging from 22.85 to 0.18 mg/mL for CRCs and 11.43 to 0.09 mg/mL for DMCRT. In addition, BAX, BID, BCL2, MYCN, SOD1, and GSTM1 gene expression was studied by qRT-PCR analysis. Both compounds demonstrated cytotoxic effects against glioblastoma and rhabdomyosarcoma cell lines, in a dose- and time-dependent manner. They induced ...

Glucocorticoids (GCs) are still first-line drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone is a corticosteroid and one of the most important agents in the treatment of ALL. We report here a study of Prednisolone treatment using as a model a leukemia cell line with subsequent investigation of resistance-related gene expression. Gene silencing has been used in order to identify significant targets of resistance to GC-induced apoptosis in ALL cells. We analyzed effects of increasing doses of Prednisolone on ALL cell survival and growth, and we monitored immediate effects on gene expression through gene expression assays. We determined Prednisolone cytotoxicity and cell cycle distribution as well as DNA content. Upon treatment with escalating Prednisolone concentration, we observed a gradual decline in cell survival. MCL1 and GRIM19 were investigated as possible genes for the intrinsic capacity of this cell line to respond to corticosteroid and a snapshot of early changes was examined. Early MCL1 and GRIM19 expression correlated significantly to late GC-induced apoptosis. Prednisolone competitively induces MCL1 expression. Consistently with previous studies on primary leukemia blasts, cells are sensitive to proteasome inhibitor MG132; no interference of Prednisolone with MG132 effects on this cell line was noted. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Antigen screening for the SARS-CoV-2 S1 spike protein is among the most promising tools for the mass monitoring of asymptomatic carriers of the virus, especially in limited resource environments. Herewith, we report on the possible use of the angiotensin-converting enzyme 2 (ACE2), the natural receptor and entry point of the virus, as a biorecognition element for the detection of the S1 antigen combined with an established bioelectric biosensor based on membrane-engineered cells. The working principle of our approach is based on the measurable change of the electric potential of membrane-engineered mammalian cells bearing ACE2 after attachment of the respective viral protein. We demonstrate that sensitive and selective detection of the S1 antigen is feasible in just three min, with a limit of detection of 20 fg/mL. In a preliminary clinical application, positive patient-derived samples were identified with a 87.9% score compared to RT-PCR. No cross-reactivity was observed against a ...

Cyclodextrins (CD) have been playing a very important role in the formulation of poorly water-soluble drugs by improving apparent drug solubility and/or dissolution. In the current study we focused on the investigation of the cytotoxic effect of cyclodextrin/Gefitinib in inclusion with three types of cyclodextrin, as well as in its inhibitory activity of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity using biological assays. The activity of Gefitinib and Gefitinib/ cyclodextrin were measured in pediatric neuroblastoma (NB) tumor cell lines. We have shown that CD/Gefitinib complexes are effective against neuroblastoma cells in vitro. Our studies provided a detailed picture of inclusion of Gefitinib in cyclodextrins and verify improved efficacy of the CD-encapsulated drug in cytotoxicity assays on pediatric tumor cell lines. An understanding of the structural details of guest inclusion in CDs may be useful in the engineering of modified guest-host preparations with o...

MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) has been one of the most studied genes in neuroblastoma. It is known for its oncogenetic mechanisms, as well as its role in the prognosis of the disease and it is considered one of the prominent targets for neuroblastoma therapy. In the present work, we attempted to review the literature, on the relation between MYCN and neuroblastoma from all possible mechanistic sites. We have searched the literature for the role of MYCN in neuroblastoma based on the following topics: the references of MYCN in the literature, the gene’s anatomy, along with its transcripts, the protein’s anatomy, the epigenetic mechanisms regulating MYCN expression and function, as well as MYCN amplification. MYCN plays a significant role in neuroblastoma biology. Its functions and properties range from the forming of G-quadraplexes, to the interaction with miRNAs, as well as the regulation of gene methylation and histone acetylation and deacetylation. Although ...

The growth arrest-specific transcript 5 (GAS5) is a >200-nt lncRNA molecule that regulates several cellular functions, including proliferation, apoptosis, invasion and metastasis, across different types of human cancers. Here, we reviewed the current literature on the expression of GAS5 in leukemia, cervical, breast, ovarian, prostate, urinary bladder, lung, gastric, colorectal, liver, osteosarcoma and brain cancers, as well as its interaction with various miRNAs and its effect on therapy-related resistance in these malignancies. The general consensus is that GAS5 acts as a tumor suppressor across different tumor types and that its up-regulation results in tumor sensitization to chemotherapy or radiotherapy. GAS5 seems to play a previously unappreciated, but significant role in tumor therapy-induced resistance.

Background: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants there is a growing interest in Crocus sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico. Objective: The present study aims to address the anti-toxicant role of Crocus sativus L. in the cases of toxin and drug toxification. Materials and Methods: An electronic literature search was conducted by the two authors from 1993 to August 2017. Original articles...

Disruption of tissue function activates cellular stress which triggers a number of mechanisms that protect the tissue from further damage. These mechanisms involve a number of homeostatic modules, which are regulated at the level of gene expression by the transactivator NF-κB. This transcription factor shifts between activation and repression of discrete, cell-dependent gene expression clusters. Some of its target genes provide feedback to NF-κB itself, thereby strengthening the inflammatory response of the tissue and later terminating inflammation to facilitate restoration of tissue homeostasis. Disruption of key feedback modules for NF-κB in certain cell types facilitates the survival of clones with genomic aberrations, and protects them from being recognized and eliminated by the immune system, to enable thereby carcinogenesis.

Background: Resistance to glucocorticoid (GC)-induced apoptosis in Acute Lymphoblastic Leukemia (ALL), is considered one of the major prognostic factors for the disease. Prednisolone is a corticosteroid and one of the most important agents in the treatment of acute lymphoblastic leukemia. The mechanics of GC resistance are largely unknown and intense ongoing research focuses on this topic. Aim: The aim of the present study is to review some aspects of GC resistance in ALL, and in particular of Prednisolone, with emphasis on previous and present knowledge on gene expression and signaling pathways playing a role in the phenomenon. Methods: An electronic literature search was conducted by the authors from 1994 to June 2019. Original articles and systematic reviews selected, and the titles and abstracts of papers screened to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: Identification of gene targets responsible for...

Although a considerable amount of knowledge is gathered concerning diseases and their transmission, still more is to learn on their mathematical modelling. The present work reviews the existent knowledge on models of epidemiological dispersion, the creation of a new form of an epidemiological diffusion equation, and the subsequent application of this equation to the investigation of epidemiological phenomena. Towards that scope, the authors have used mathematical models which have been previously reported, as well as algorithmic approaches of stochastic nature for the solution of complex functions. In particular, they have used dynamic programming algorithms, Robbins-Monro and Kiefer-Wolfowitz stochastic optimization algorithms, Markov chains and cellular automata. The modified diffusion equation could potentially provide a useful tool to the investigation of epidemiological phenomena. More research is required in order to explore the extent of its possibilities and uses.

Abstract Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Dysregulation of adipokine pathways is implicated in the carcinogenesis and ALL. The aim of this study is to present the most recent data available regarding the role of leptin, adiponectin and ghrelin in the pathogenesis and prognosis of ALL. The PubMed database was searched using ‘Leptin’, ‘Adiponectin’, ‘Ghrelin’, ‘Cancer’, ‘Children’ and ‘Acute Lymphoblastic Leukemia’ as keywords. The majority of the studies indicated that leptin levels are increased and adiponectin levels are decreased in ALL children at diagnosis, as well as in ALL survivors. Ghrelin levels were found to be lower at diagnosis and progressively increased during treatment. Further research is warranted, as the heterogeneity of the current studies, various treatment protocols and differences in sample sizes make it difficult to deduce solid conclusions regarding the role of adipokines in ALL.

Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants there is growing interest in Crocus Sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico. The present study aims to address the anti-toxicant role of Crocus Sativus L. in the case of cardiovascular disease and its role towards the cardioprotective role of Crocus Sativus L. An electronic literature search was conducted by the two authors from 1993 to August 2017. Orig...

Cancer is a growing problem because it is a chronic disease that affects, not only patient health, but also its daily living. Concurrent cancer therapies have ameliorated cancer prevalence, but the severity and frequency of toxicity and side effects during therapy have led the scientific community to rediscover the possible therapeutic effectiveness of herbs and spices. Crocus sativus L., commonly known as saffron, has been used in folk medicine for centuries. Today, data from numerous in vivo and in vitro studies support its anti-cancer activity, making it a promising anti-cancer agent for study. In the present review, we focus on the anti-cancer activity of C. sativus and its derivates. Medications that are currently used as chemotherapeutic or anti-cancer agents are associated with side effects whether used at effective doses or at levels that exceed the therapeutic dose. Therefore, many cancer survivors suffer from serious and even life-threatening long- or short-term sequelae, so the development of alternative/coadjutant drugs is imperative.

Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants there is growing interest in Crocus Sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico. The present study aims to address the protective role of Crocus Sativus L. in neurodegeneration with emphasis in Parkinson's and Alzheimer's disease. An electronic literature search was conducted by two of the authors from 1993 to August 2017. Original articles and syste...

The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increa...

Background:: Tumors of the childhood are considered to be grave and devastating pathologies, with high mortality rates. Current therapeutic options like cytotoxic drugs and radiotherapy target both healthy and malignant cells, thus resulting in long-term neurological and intellectual sequelae and endocrinological disorders. Objectives:: In this study, we focused on the anticancer potency of crocins, the main constituents of Crocus sativus L, stigmas. Crocins were first extracted using organic solvents from the dried stigmas and then were identified using the HPLC analysis. Materials and Methods:: TE-671 cells were treated with the extract of crocins using a range of concentrations between 0.25-mg/ mL and 16 mg/mL. Viability of the cells was measured at 24h, 48h, 72h and 96h. In addition, we have examined the expression levels of the p53 gene using Real-Time Reverse Transcription PCR. Results:: Results showed that crocins exerted significant cytotoxic and anti-proliferative effects i...

This work was undertaken to investigate the efficacy of gefitinib, an EGFR tyrosine kinase inhibitor, in tumor cell lines of the CNS by studying cell proliferation and phosphorylation of the tyrosine kinase domain of The study included neuroblastoma (SHSY5Y) and glioblastoma (A172) cell lines. The MTT cell proliferation assay was performed in order to quantify the cytotoxic effect of gefitinib in A172 and SH-SY5Y cells, whilst ELISA assay was used to assess the effect on the phosphorylation of tyrosine residue 1068 of EGFR. As the concentration of gefitinib increased, MTT conversion into formazan was observed to progressively decrease, confirming the cytotoxic activity of gefitinib. In the ELISA assay for both cell lines investigated, as the dose of gefitinib increased, a gradual decrease in EGFR tyrosine phosphorylation was detected. The findings of the current study could form the basis of research regarding the use of novel inhibitors in the treatment of solid tumors in pediatric patients and a shift to targeted therapy with higher efficacy and fewer side effects.