Effects of curcumin and its adjuvant on TPC1 thyroid cell line.
Publication Date: 30/03/2019, on Chemico-biological interactions
by Esposito T, Lucariello A, Hay E, Contieri M, Tammaro P, Varriale B, Guerra G, De Luca A, Perna A
Previous studies have demonstrated that different curcumin extracts are able to influence cell metabolic activity vitality in human papillary thyroid carcinoma TPC-1 cells. We continued the study using the most effective extract and adding other nutraceuticals such as piperine and vitamin E, in order to define the possible role of these in modulating the genetic expression of cell markers and to understand the effectiveness in modulating the regression of cancer phenotype. Cells were treated with one extract of curcumin (Naturex Ultimate Botanical Benefits), with Piperine (Piper Longum, A.C.E.F.) and Vitamin E (Dry Vitamin E-Acetate 50% DC, BASF) alone and in combination, dissolved in the culture medium, for 48 h. Treatment with the different nutraceuticals is able to influence cell cycle regulators (cyclin D1, β-catenin, p21, p53) and activators or inhibitors of apoptosis (BAX, pro-caspase3, Bcl-2). They are able to influence cell cycle distribution and metabolic activity vitality. The inhibitory effect of curcumin, piperine and vitamin E on cell proliferation involves different markers, and in particular inhibits β-catenin, cyclinD1 and p53, making them candidates for a possible use in alternative therapies although further studies are needed.
Native Ion Mobility Mass Spectrometry: When Gas-Phase Ion Structures Depend on the Electrospray Charging Process.
Publication Date: 28/03/2019, on Journal of the American Society for Mass Spectrometry
by Khristenko N, Amato J, Livet S, Pagano B, Randazzo A, Gabelica V
Ion mobility spectrometry (IMS) has become popular to characterize biomolecule folding. Numerous studies have shown that proteins that are folded in solution remain folded in the gas phase, whereas proteins that are unfolded in solution adopt more extended conformations in the gas phase. Here, we discuss how general this tenet is. We studied single-stranded DNAs (human telomeric cytosine-rich sequences with CCCTAA repeats), which fold into an intercalated motif (i-motif) structure in a pH-dependent manner, thanks to the formation of C-H-C base pairs. As i-motif formation is favored at low ionic strength, we could investigate the ESI-IMS-MS behavior of i-motif structures at pH ~ 5.5 over a wide range of ammonium acetate concentrations (15 to 100 mM). The control experiments consisted of either the same sequence at pH ~ 7.5, wherein the sequence is unfolded, or sequence variants that cannot form i-motifs (CTCTAA repeats). The surprising results came from the control experiments. We found that the ionic strength of the solution had a greater effect on the compactness of the gas-phase structures than the solution folding state. This means that electrosprayed ions keep a memory of the charging process, which is influenced by the electrolyte concentration. We discuss these results in light of the analyte partitioning between the droplet interior and the droplet surface, which in turn influences the probability of being ionized via a charged residue-type pathway or a chain extrusion-type pathway.
Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform.
Publication Date: 28/03/2019, on International journal of molecular sciences
by Aliperti V, Sgueglia G, Aniello F, Vitale E, Fucci L, Donizetti A
EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.
Brain Metabolic DNA Is Reverse Transcribed in Cytoplasm: Evidence by Immunofluorescence Analysis.
Publication Date: 27/03/2019, on Molecular neurobiology
by Prisco M, Casalino J, Cefaliello C, Giuditta A
In a previous study (Mol Neurobiol 55:7476-7486, 2017), newly synthesized brain metabolic DNA (BMD) from rat subcellular fractions has been shown to behave as a DNA-RNA hybrid when analyzed in cesium gradients at early [H] thymidine incorporation times but to assume the double-stranded configuration at later times. Conversely, BMD from purified nuclei displayed the dsDNA configuration even at early incorporation times. The results were interpreted to support the BMD origin by reverse transcription in the cytoplasm and its later acquisition of the double-stranded configuration before the partial transfer to the nuclei. This interpretation has now been confirmed by immunofluorescence analyses of newly synthesized BrdU-labeled BMD from the mouse brain that demonstrates its cytoplasmic localization and colocalization with DNA-RNA hybrids. In addition, BrdU-labeled BMD has been shown to colocalize with astroglial anti-GFAP antibodies and with presynaptic anti-synaptophysin antibodies.
Circulating factors present in the sera of naturally skinny people may influence cell commitment and adipocyte differentiation of mesenchymal stromal cells.
Publication Date: 26/03/2019, on World journal of stem cells
by Alessio N, Squillaro T, Monda V, Peluso G, Monda M, Melone MA, Galderisi U, Di Bernardo G
Research on physiopathology of obesity may receive new hints from studies on skinny people (SP). These are individuals who show a poor or null gaining of body weight, in spite of high-calorie intake, by far exceeding the body requirements.
Assessing Anxiety and its correlates in Amyotrophic Lateral Sclerosis: the State-Trait Anxiety Inventory.
Publication Date: 21/03/2019, on Muscle & nerve
by Siciliano M, Trojano L, Trojsi F, Monsurrò MR, Tedeschi G, Santangelo G
We evaluated: i) psychometric properties of State-Trait Anxiety Inventory Form Y (STAI Form Y); ii) clinical correlates of state and trait anxiety; iii) associations of anxiety with Quality of Life (QoL) dimensions.
Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction.
Publication Date: 16/03/2019, on Antioxidants (Basel, Switzerland)
by La Russa D, Giordano F, Marrone A, Parafati M, Janda E, Pellegrino D
Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress.
Stability is not everything the case of the cyclization of the thrombin binding aptamer.
Publication Date: 12/03/2019, on Chembiochem : a European journal of chemical biology
by Riccardi C, Meyer A, Vasseur JJ, Russo Krauss I, Paduano L, Oliva R, Petraccone L, Morvan F, Montesarchio D
Aiming at novel approaches to obtain improved aptamers, we developed a cyclic TBA analogue (cycTBA) by exploiting a Cu(I)-assisted azide-alkyne cycloaddition. Its markedly increased serum resistance and exceptional thermal stability of its G-quadruplex vs. TBA were associated to halved thrombin inhibition, suggesting that some flexibility in TBA structure is necessary for protein recognition.
A Fast Detection Strategy for Cyanobacterial blooms and associated cyanotoxins (FDSCC) reveals the occurrence of lyngbyatoxin A in campania (South Italy).
Publication Date: 08/03/2019, on Chemosphere
by Esposito G, Teta R, Marrone R, De Sterlich C, Casazza M, Anastasio A, Lega M, Costantino V
Fast Detection Strategy for Cyanobacterial blooms and associated Cyanotoxins (FDSCC) is a multidisciplinary strategy that allows early detection, in 24 man-hours, of cyanobacteria and related cyanotoxins in water and bivalve samples. This approach combines the advantages of remote/proximal sensing with those of analytical/bioinformatics analyses, namely, LC-HRMS-based molecular networking. The detection of Lyngbyatoxin A, a lipophilic cyanotoxin, in all analyzed water samples and in bivalves, commonly used as food, was the proof of the reliability of the new method.
Persisting Embryonal Infundibular Recess in Morning Glory Syndrome: Clinical Report of a Novel Association.
Publication Date: 07/03/2019, on AJNR. American journal of neuroradiology
by D'Amico A, Ugga L, Cuocolo R, Cirillo M, Grandone A, Conforti R
Morning glory syndrome is characterized by a congenital optic disc defect that resembles the eponymous flower. We present the MR imaging findings of 2 pediatric patients with morning glory disc anomaly and persisting embryonal infundibular recess, another rare malformative finding, a previously unreported association. Neuroradiologists should be aware of the possible presence of a persisting embryonal infundibular recess in patients with morning glory syndrome, to aid in the differential diagnosis including other pituitary malformations such as pituitary stalk duplication.
Low doses of Bisphenol A have pro-inflammatory and pro-oxidant effects, stimulate lipid peroxidation and increase the cardiotoxicity of Doxorubicin in cardiomyoblasts.
Publication Date: 07/03/2019, on Environmental toxicology and pharmacology
by Quagliariello V, Coppola C, Mita DG, Piscopo G, Iaffaioli RV, Botti G, Maurea N
Endocrine disrupters are strictly associated to cancer and several cardiovascular risk factors. Bisphenol A (BPA) is an endocrine disrupter commonly used in the manufacturing of plastics based on polycarbonate, polyvinyl chloride and resins. Our study aims to investigate whether BPA may cause pro-oxidative and pro-inflammatory effects on cardiomyoblasts, thus exacerbating the Doxorubicin (DOXO)-induced cardiotoxicity phenomena. We tested the metabolic effects of BPA at low doses analyzing its affections on the intracellular calcium uptake, oxidative stress, lipid peroxidation and production of nitric oxide and interleukins. Co-incubation of BPA and DOXO significantly reduced the cardiomyoblast viability, compared to only DOXO exposure cells. The mechanisms underlying these effects are based on the stimulation of the intracellular calcium accumulation and lipid peroxidation. Notably, BPA increase the production of pro-inflammatory interleukins involved in cardiovascular diseases as well as in DOXO-Induced cardiotoxicity phenomena. This study provides a rationale for translational studies in the field of cardio-oncology.
Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients.
Publication Date: 06/03/2019, on International journal of molecular sciences
by D'Onofrio N, Pieretti G, Ciccarelli F, Gambardella A, Passariello N, Rizzo MR, Barbieri M, Marfella R, Nicoletti G, Balestrieri ML, Sardu C
The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin ( < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.
Evolution of an insect immune barrier through horizontal gene transfer mediated by a parasitic wasp.
Publication Date: 05/03/2019, on PLoS genetics
by Di Lelio I, Illiano A, Astarita F, Gianfranceschi L, Horner D, Varricchio P, Amoresano A, Pucci P, Pennacchio F, Caccia S
Genome sequencing data have recently demonstrated that eukaryote evolution has been remarkably influenced by the acquisition of a large number of genes by horizontal gene transfer (HGT) across different kingdoms. However, in depth-studies on the physiological traits conferred by these accidental DNA acquisitions are largely lacking. Here we elucidate the functional role of Sl gasmin, a gene of a symbiotic virus of a parasitic wasp that has been transferred to an ancestor of the moth species Spodoptera littoralis and domesticated. This gene is highly expressed in circulating immune cells (haemocytes) of larval stages, where its transcription is rapidly boosted by injection of microorganisms into the body cavity. RNAi silencing of Sl gasmin generated a phenotype characterized by a precocious suppression of phagocytic activity by haemocytes, which was rescued when these immune cells were incubated in plasma samples of control larvae, containing high levels of the encoded protein. Proteomic analysis demonstrated that the protein Sl gasmin is released by haemocytes into the haemolymph, where it opsonizes the invading bacteria to promote their phagocytosis, both in vitro and in vivo. Our results show that important physiological traits do not necessarily originate from evolution of pre-existing genes, but can be acquired by HGT events, through unique pathways of symbiotic evolution. These findings indicate that insects can paradoxically acquire selective advantages with the help of their natural enemies.
French validation of the questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS).
Publication Date: 04/03/2019, on Parkinsonism & related disorders
by Marques A, Vidal T, Pereira B, Benchetrit E, Socha J, Pineau F, Elbaz A, Artaud F, Mangone G, You H, Cormier F, Galitstky M, Pomies E, Rascol O, Derkinderen P, Weintraub D, Corvol JC, Durif F,
The management of impulse control disorders (ICDs) in Parkinson's disease (PD) relies on their early identification, allowing adjustment of antiparkinsonian treatment before these manifestations lead to major social, financial or legal consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) is an English-developed and -validated PD-specific rating scale constructed to support the rating of ICDs and related disorders and the assessment of changes in symptom severity over time, but it has not to date been validated in French.
A signalling cascade involving receptor-activated phospholipase A<sub>2</sub>, glycerophosphoinositol 4-phosphate, Shp1 and Src in the activation of cell motility.
Publication Date: 01/03/2019, on Cell communication and signaling : CCS
by Varone A, Mariggiò S, Patheja M, Maione V, Varriale A, Vessichelli M, Spano D, Formiggini F, Lo Monte M, Brancati N, Frucci M, Del Vecchio P, D'Auria S, Flagiello A, Iannuzzi C, Luini A, Pucci P, Banci L, Valente C, Corda D
Shp1, a tyrosine-phosphatase-1 containing the Src-homology 2 (SH2) domain, is involved in inflammatory and immune reactions, where it regulates diverse signalling pathways, usually by limiting cell responses through dephosphorylation of target molecules. Moreover, Shp1 regulates actin dynamics. One Shp1 target is Src, which controls many cellular functions including actin dynamics. Src has been previously shown to be activated by a signalling cascade initiated by the cytosolic-phospholipase A (cPLA) metabolite glycerophosphoinositol 4-phosphate (GroPIns4P), which enhances actin polymerisation and motility. While the signalling cascade downstream Src has been fully defined, the mechanism by which GroPIns4P activates Src remains unknown.