Ruminant meat and milk contain δ-valerobetaine, another precursor of trimethylamine N-oxide (TMAO) like γ-butyrobetaine.
Publication Date: 15/09/2018, on Food chemistry
by Servillo L, D'Onofrio N, Giovane A, Casale R, Cautela D, Castaldo D, Iannaccone F, Neglia G, Campanile G, Balestrieri ML
Quaternary ammonium compounds containing N-trimethylamino moiety, such as choline derivatives and carnitine, abundant in meat and dairy products, are metabolic precursors of trimethylamine (TMA). A similar fate is reported for N-trimethyllysine and γ-butyrobetaine. With the aim at investigating the metabolic profile of such metabolites in most employed animal dietary sources, HPLC-ESI-MS/MS analyses on ruminant and non-ruminant milk and meat were performed. Results demonstrate, for the first time, the presence of δ-valerobetaine, occurring at levels higher than γ-butyrobetaine in all ruminant samples compared to non-ruminants. Demonstration of δ-valerobetaine metabolic origin, surprisingly, showed that it originates from rumen through the transformation of dietary N-trimethyllysine. These results highlight our previous findings showing the ubiquity of free N-trimethyllysine in vegetable kingdom. Furthermore, δ-valerobetaine, similarly to γ-butyrobetaine, can be degraded by host gut microbiota producing TMA, precursor of the proatherogenic trimethylamine N-oxide (TMAO), unveiling its possible role in the biosynthetic route of TMAO.
Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity.
Publication Date: 14/09/2018, on Nutrients
by Quagliariello V, Vecchione R, Coppola C, Di Cicco C, De Capua A, Piscopo G, Paciello R, Narciso V, Formisano C, Taglialatela-Scafati O, Iaffaioli RV, Botti G, Netti PA, Maurea N
Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35⁻40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35⁻40% and increased IL-10 production by 25⁻27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.
Integrated Cognitive and Neuromotor Rehabilitation in Multiple Sclerosis: A Pragmatic Study.
Publication Date: 05/09/2018, on Frontiers in behavioral neuroscience
by Barbarulo AM, Lus G, Signoriello E, Trojano L, Grossi D, Esposito M, Costabile T, Lanzillo R, Saccà F, Morra VB, Conchiglia G
Few studies examined the effects of combined motor and cognitive rehabilitation in patients with multiple sclerosis (MS). The present prospective, multicenter, observational study aimed to determine the efficacy of an integrated cognitive and neuromotor rehabilitation program versus a traditional neuromotor training on walking, balance, cognition and emotional functioning in MS patients. Sixty three MS patients were selected and assigned either to the Integrated Treatment Group (ITG; = 32), receiving neuropsychological treatment (performed by ERICA software and paper-pencil tasks) complemented by conventional neuromotor rehabilitation, or to the Motor Treatment Group ( = 31) receiving neuromotor rehabilitation only. The intervention included two 60-min sessions per week for 24 weeks. At baseline and at end of the training all patients underwent a wide-range neuropsychological, psychological/emotional, and motor assessment. At baseline the two groups did not differ for demographic, neuropsychological, psychological/emotional, and motor features significantly. After rehabilitation, only ITG group significantly ( for False Discovery Rate) improved on test tapping spatial memory, attention and cognitive flexibility, as well as on scales assessing depression and motor performance (balance and gait). A regression analysis showed that neuropsychological and motor improvement was not related to improvements in fatigue and depression. The present study demonstrated positive effects in emotional, motor, and cognitive aspects in MS patients who received an integrated cognitive and neuromotor training. Overall, results are supportive of interventions combining motor and cognitive training for MS.
Dihydroartemisinin induces apoptosis and autophagy-dependent cell death in cholangiocarcinoma through a DAPK1-BECLIN1 pathway.
Publication Date: 22/08/2018, on Molecular carcinogenesis
by Thongchot S, Vidoni C, Ferraresi A, Loilome W, Yongvanit P, Namwat N, Isidoro C
Cholangiocarcinoma (CCA) is a very aggressive cancer arising from the malignant transformation of cholangiocytes. Intrahepatic CCA is associated with reactive inflammation and intense fibrosis of the hepatobiliary tract. Dihydroartemisinin (DHA), the active compound found in Artemisia annua, has been shown to possess anti-tumor activity in a variety of human cancers, including hepatoma. Here, we tested the ability of DHA to specifically kill CCA cells and have investigated the underlying mechanisms. DHA induced both apoptosis and autophagy-dependent caspase-independent cell death in many CCA cell lines, while being slightly toxic to immortalized cholangiocytes. DHA induced the expression of many apoptosis- and autophagy-related genes in CCA cells. In particular, it greatly induced the expression of DAPK1, and reduced the interaction of BECLIN1 with BCL-2 while promoting its interaction with PI3KC3. Genetic silencing of DAPK1 prevented DHA-induced autophagy. Pharmacologic and genetic inhibition of BECLIN1 function prevented autophagy and cell death induced by DHA in CCA cells. These data unravel a novel pathway of DHA cancer toxicity and open the possibility to introduce DHA in the therapeutic regimen for the treatment of CCA. This article is protected by copyright. All rights reserved.
Inflammatory Cytokines and SIRT1 Levels in Subcutaneous Abdominal Fat: Relationship With Cardiac Performance in Overweight Pre-diabetics Patients.
Publication Date: 21/08/2018, on Frontiers in physiology
by Sardu C, Pieretti G, D'Onofrio N, Ciccarelli F, Paolisso P, Passavanti MB, Marfella R, Cioffi M, Mone P, Dalise AM, Ferraraccio F, Panarese I, Gambardella A, Passariello N, Rizzo MR, Balestrieri ML, Nicoletti G, Barbieri M
In obese patients the superficial adipose tissue expresses cytokines, and sirtuins, that may affect myocardial function. In this study, we investigated the effect of metformin therapy added to a hypocaloric diet on the inflammatory pattern and cardiac performance (MPI) in obese patients with pre-diabetic condition. Fifty-eight obese patients that were enrolled for abdominoplastic surgery were divided into patients with pre-diabetic condition (n 40) and normo-glycemic patients (n18). Patients with pre-diabetic condition were randomly assigned to metformin therapy added to a hypocaloric diet (group 1, n 20) or to a hypocaloric diet therapy alone (group 2, n20). Patients with normo-glycemic condition were assigned to a hypocaloric diet therapy. During enrollment, obese patients with a pre-diabetic condition (group 1 and 2) presented higher glucose values, lower values of insulin, and higher values of the homeostasis model for the assessment of insulin resistance (HOMA-IR) than obese patients with normo-glycemic condition(group 3). In addition, they had higher values of C Reactive protein (CRP), interleukin 6 (IL6), and lower values of sirtuin 1(SIRT1). In the 12th month of the follow-up, metformin therapy induced in patients with pre-diabetic condition (group 1) a significant reduction of glucose values, HOMA-IR, and inflammatory markers such as CRP (1.04 ± 0.48 vs. 0.49 ± 0.02 mmol/L, < 0.05), IL6 (4.22 ± 0.45 vs. 3.33 ± 0.34 pg/ml, < 0.05), TNFα (6.95 ± 0.59 vs. 5.15 ± 0.44 pg/ml, < 0.05), and Nitrotyrosine (5,214 ± 0,702 vs. 2,151 ± 0,351 nmol/l, < 0.05). This was associated with a significant reduction of Intima-media thickness (1.01 ± 0.15 vs. 0.86 ± 0.15 mm, < 0.05), Septum (14 ± 2.5 vs. 10.5 ± 2 mm, < 0.05), Posterior wall (11 ± 1.5 vs. 8 ± 1 mm, < 0.05), LV mass (192.5 ± 49.5 vs. 133.2 ± 37.6 g, < 0.05) and of MPI (0.58 ± 0.03 vs. 0.38 ± 0.02, < 0.05). At 12 months of follow-up, group 2 experienced only a reduction of cholesterol (4.15 ± 0.94 vs. 4.51 ± 0.88 mmol/L, < 0.05) and triglycerides (1.71 ± 1.18 vs. 1.83 ± 0.54 mmol/L, < 0.05). At 12 months of follow-up, group 3 experienced a significant reduction of inflammatory markers, and also of echographic parameters, associated with amelioration of myocardial performance. To date, IL6 expression was related to higher values of left ventricle mass (-value 0.272, -value 0.039), and to higher IMT (-value 0.272, -value 0.039), such as those observed for CRP (-value 0.308, -value 0.021), for glucose blood values (-value 0.449, -value 0.001), and for HOMA-IR (-value 0.366, -value 0.005). An inverse correlation was found between subcutaneous fat expression of SIRT1 and myocardial performance index (-value-0.236, -value 0.002). In obese patients with pre-diabetic condition a metformin therapy may reduce inflammation and oxidative stress, and this may be associated with the amelioration of the cardiac performance. Clinical research trial number: NCT03439592.
Isolation of Smenopyrone, a Bis-γ-Pyrone Polypropionate from the Caribbean Sponge <i>Smenospongia aurea</i>.
Publication Date: 17/08/2018, on Marine drugs
by Esposito G, Teta R, Della Sala G, Pawlik JR, Mangoni A, Costantino V
The organic extract of the Caribbean sponge has been shown to contain an array of novel chlorinated secondary metabolites derived from a mixed PKS-NRPS biogenetic route such as the smenamides. In this paper, we report the presence of a biogenetically different compound known as smenopyrone, which is a polypropionate containing two γ-pyrone rings. The structure of smenopyrone including its relative and absolute stereochemistry was determined by spectroscopic analysis (NMR, MS, ECD) and supported by a comparison with model compounds from research studies. Pyrone polypropionates are unprecedented in marine sponges but are commonly found in marine mollusks where their biosynthesis by symbiotic bacteria has been hypothesized and at least in one case demonstrated. Since pyrones have recently been recognized as bacterial signaling molecules, we speculate that smenopyrone could mediate inter-kingdom chemical communication between and its symbiotic bacteria.
Minimally Invasive and Portable Method for the Identification of Proteins in Ancient Paintings.
Publication Date: 15/08/2018, on Analytical chemistry
by Cicatiello P, Ntasi G, Rossi M, Marino G, Giardina P, Birolo L
A novel method for the analysis of proteinaceous materials present on painted surfaces was developed by taking advantage of the adhesive ability of some fungal proteins which can form a stable and homogeneous layer on flexible transparency sheets able to capture trypsin in a fully active form. We demonstrated that the bioactive sheets were able to efficiently digest proteins, present as such, on surfaces of painted tests and historical samples, releasing peptides that can allow an easy and confident identification of the proteinaceous binders by standard bottom-up proteomic approach. By this method there is no need: (i) to transport the artifacts and (ii) to remove, even at micro level, a sample from the object. The ingenuity of the method lies in the easily accommodated sampling coupled with a minimal invasiveness.
Getting value from the waste: recombinant production of a sweet protein by Lactococcus lactis grown on cheese whey.
Publication Date: 15/08/2018, on Microbial cell factories
by Boumaiza M, Colarusso A, Parrilli E, Garcia-Fruitós E, Casillo A, Arís A, Corsaro MM, Picone D, Leone S, Tutino ML
Recent biotechnological advancements have allowed for the adoption of Lactococcus lactis, a typical component of starter cultures used in food industry, as the host for the production of food-grade recombinant targets. Among several advantages, L. lactis has the important feature of growing on lactose, the main carbohydrate in milk and a majoritarian component of dairy wastes, such as cheese whey.
Novel use of Evolved Gas Analysis/Mass Spectrometry to identify the earliest organic binder in Aegean style wall paintings from Tel Kabri, Israel, dated to the late 18th C. B.C.E.
Publication Date: 10/08/2018, on Angewandte Chemie (International ed. in English)
by Linn R, Bonaduce I, Ntasi G, Birolo L, Yasur-Landau A, Cline E, Nevin A, Lluveras-Tenorio A
An organic binder was identified in the painted fragments from the Canaanite palace of Tel Kabri, Israel. Recently dated to the late 18th C. B.C.E. by 14C, Tel Kabri is the most ancient of the Eastern Mediterranean sites in which Aegean style paintings have been found. The application of pigments was suspected to be using an organic binding medium, particularly for the Egyptian Blue pigment. Samples of blue paint were examined using Evolved Gas Analysis/Mass Spectrometry (EGA-MS) in order to overcome the analytical challenge imposed by highly degraded aged proteinaceous materials. Egg was identified as the binder based on the presence of Hexadecanonitrile and octadecanonitrile confirming the use of a secco painting technique. Lysozyme C from Gallus gallus was detected by proteomics analysis, confirming the presence of egg. To the authors' knowledge, this is the earliest use of egg as a binder in Aegean style wall paintings.
Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins.
Publication Date: 09/08/2018, on International journal of molecular sciences
by Monti M, De Rosa V, Iommelli F, Carriero MV, Terlizzi C, Camerlingo R, Belli S, Fonti R, Di Minno G, Del Vecchio S
Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis. We found that high levels of α5β1, αvβ3 and αvβ5 enhance cell adhesion to NETs, whereas low expression of α5β1 prevents cell attachment to NETs. Excess of cyclic RGD peptide inhibited cell adhesion to NETs by competing with fibronectin within NETs. The maximal reduction of such adhesion was similar to that obtained by DNase 1 treatment causing DNA degradation. Our findings indicate that NETs from neutrophil-like cells may be used as a substrate for large screening of the adhesion properties of cancer cells expressing a variety of RGD-binding integrins.
HMGB1 binds to the KRAS promoter G-quadruplex: a new player in oncogene transcriptional regulation?
Publication Date: 06/08/2018, on Chemical communications (Cambridge, England)
by Amato J, Madanayake TW, Iaccarino N, Novellino E, Randazzo A, Hurley LH, Pagano B
This communication reports on a possible distinct role of HMGB1 protein. Biophysical studies revealed that HMGB1 binds and stabilizes the G-quadruplex of the KRAS promoter element that is responsible for most of the transcriptional activity. Biological data showed that inhibition of HMGB1 increases KRAS expression. These results suggest that HMGB1 could play a role in the gene transcriptional regulation via the functional recognition of the G-quadruplex.
Bullying at Workplace and Brain-Imaging Correlates.
Publication Date: 04/08/2018, on Journal of clinical medicine
by Nolfe G, Cirillo M, Iavarone A, Negro A, Garofalo E, Cotena A, Lazazzara M, Zontini G, Cirillo S
The relationship between psychosocial stress at work and mental health outcome is well-known. Brain-imaging studies hypothesize morphological brain modifications connected to work-related stress. To our knowledge this is the first study describing the link between work characteristics and brain imaging in a sample of work-related psychiatric patients assessed according to standardized clinical and diagnostic criteria. The aims of the study are: (1) to evaluate hippocampal and whole brain volumes in work-related psychiatric disturbances; (2) to verify the relationship between brain changes and the anxious and/or depressive symptoms; (3) to observe the relationship between the brain changes and the degree of the bullying at workplace. The hippocampus and whole brain volumes of 23 patients with work-related adjustment-disorders were compared with 15 controls by means of MRI. MR images highlight a smaller hippocampal volume in patients compared with controls. Significant reduction in the patients' gray matter was found in three brain areas: right inferior temporal gyrus, left cuneus, left inferior occipital gyrus. The reduction of the hippocampi volumes was related to work distress and, above all, to bullying at workplace. The results confirm that the morphological brain abnormalities could be involved in work-related psychiatric disturbances.
Visual pursuit of one's own face in disorders of consciousness: a quantitative analysis.
Publication Date: 30/07/2018, on Brain injury
by Trojano L, Moretta P, Masotta O, Loreto V, Estraneo A
Eye behaviour is important to distinguish minimally conscious state (MCS) from vegetative state (VS).
Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.
Publication Date: 25/07/2018, on Multiple sclerosis (Houndmills, Basingstoke, England)
by Saccà F, Lanzillo R, Signori A, Maniscalco GT, Signoriello E, Lo Fermo S, Repice A, Annovazzi P, Baroncini D, Clerico M, Binello E, Cerqua R, Mataluni G, Bonavita S, Lavorgna L, Zarbo IR, Laroni A, Rossi S, Pareja Gutierrez L, La Gioia S, Frigeni B, Barcella V, Frau J, Cocco E, Fenu G, Torri Clerici V, Sartori A, Rasia S, Cordioli C, Di Sapio A, Pontecorvo S, Grasso R, Barrilà C, Russo CV, Esposito S, Ippolito D, Bovis F, Gallo F, Sormani MP,
With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.
Organization of GPI-anchored proteins at the cell surface and its physiopathological relevance.
Publication Date: 24/07/2018, on Critical reviews in biochemistry and molecular biology
by Lebreton S, Zurzolo C, Paladino S
Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of proteins attached to the extracellular leaflet of the plasma membrane via a post-translational modification, the glycolipid anchor. The presence of both glycolipid anchor and protein portion confers them unique features. GPI-APs are expressed in all eukaryotes, from fungi to plants and animals. They display very diverse functions ranging from enzymatic activity, signaling, cell adhesion, cell wall metabolism, neuritogenesis, and immune response. Likewise other plasma membrane proteins, the spatio-temporal organization of GPI-APs is critical for their biological activities in physiological conditions. In this review, we will summarize the latest findings on plasma membrane organization of GPI-APs and the mechanism of its regulation in different cell types. We will also examine the involvement of specific GPI-APs namely the prion protein PrP, the Folate Receptor alpha and the urokinase plasminogen activator receptor in human diseases focusing on neurodegenerative diseases and cancer.