Nicotinaldehyde, a Novel Precursor of NAD Biosynthesis, Abrogates the Anti-Cancer Activity of an NAD-Lowering Agent in Leukemia.

Targeting NAD depletion in cancer cells has emerged as an attractive therapeutic strategy for cancer treatment, based on the higher reliance of malignant vs. healthy cells on NAD to sustain their aberrant proliferation and altered metabolism. NAD depletion is exquisitely observed when NAMPT, a key enzyme for the biosynthesis of NAD, is inhibited. Growing evidence suggests that alternative NAD sources present in a tumor environment can bypass NAMPT and render its inhibition ineffective. Here, we report the identification of nicotinaldehyde as a novel precursor that can be used for NAD biosynthesis by human leukemia cells. Nicotinaldehyde supplementation replenishes the intracellular NAD level in leukemia cells treated with NAMPT inhibitor APO866 and prevents APO866-induced oxidative stress, mitochondrial dysfunction and ATP depletion. We show here that NAD biosynthesis from nicotinaldehyde depends on NAPRT and occurs via the Preiss-Handler pathway. The availability of nicotinaldehyde in a tumor environment fully blunts the antitumor activity of APO866 in vitro and in vivo. This is the first study to report the role of nicotinaldehyde in the NAD-targeted anti-cancer treatment, highlighting the importance of the tumor metabolic environment in modulating the efficacy of NAD-lowering cancer therapy

IL-17A Expression Is Localised to Both Mononuclear and Polymorphonuclear Synovial Cell Infiltrates

This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements.IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+ (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct visualisation at arthroscopy. Synovial infiltration was assessed using immunohistochemistry for cell specific markers. Peripheral blood mononuclear and polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic conditions. IL-17A and IL-6 were quantified as above in culture supernatants.IL-17A expression was localised to mononuclear and polymorphonuclear (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A positivity was highest on CD15+ neutrophils, followed by mast cells and then CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated with sublining CD68 expression (r = 0.618, p<0.01). IL-17A SF levels correlated with IL-6 SF levels (r = 0.675, p<0.01). Patients categorized according to tp0(2)< or >20 mmHg, showed those with low tp0(2)<20 mmHg had significantly higher IL-17A+ mononuclear cells with no difference observed for PMNs. Exposure of mononuclear and polymorphonuclear cells to 3% hypoxia, significantly induced IL-6 in mononuclear cells, but had no effect on IL-17A expression in mononuclear and polymorphonuclear cells.This study demonstrates IL-17A expression is localised to several immune cell subtypes within the inflamed synovial tissue, further supporting the concept that IL-17A is a key mediator in inflammatory arthritis. The association of hypoxia with Il-17A expression appears to be indirect, probably through hypoxia-induced pro-inflammatory pathways and leukocyte influx within the joint microenvironment

Seta

L'origine della seta si fa risalire al 1958 il percorso storico è stato trattato con particolare attenzione per definire più accuratamente tutto il processo della sua lavorazione.La seta è stata anche trattata da un punto di vista commerciale, importanti sono i suoi impieghi come importante è la sua qualità sia dal punto di vista della tessitura sia da un punto di vista della provenienza. Il comparto industriale riveste infine un'interesse sia sociale che economic

Dinamiche del Settore Cosmetico in Italia

La proiezione delle previsioni per l’industria cosmetica nel 2013 propone un andamento ancora in crescita per quanto riguarda il fatturato delle aziende, cioè il valore della produzione. Si prevede che alla fine dell’anno verrà superata la soglia dei 9.200 milioni di euro di sell-in ( Beauty Report, 2013), con un tasso positivo di oltre due punti percentuali. Le esportazioni del settore sono attese in crescita del 12%, con un valore superiore ai 3.000 milioni di euro, a conferma della competitività dell’offerta italiana sui mercati internazionali. Il lavoro ha preso in considerazione alcuni importanti aspetti relativi al settore della cosmesi, quali: ritorno degli investimenti, in particolare sulla ricerca e sviluppo, problemi legati alla tipologia dei canali distributivi, maggiore attenzione al biologico e al naturale, come anche alla sicurezza, in relazione sia al prodotto che al packaging, rafforzamento delle iniziative d'internazionalizzazione, miglioramenti dei rapporti tra i diversi segmenti della filiera

IL CONTESTO ENERGETICO-AMBIENTALE E LE POTENZIALITA'POLITICHE ED ECONOMICHE DELLE TECNOLOGIE SOLARI "PV" NEI P.V.S.

Electric energy must be considered a strategic variable capable of improving the levels of social and environmental quality through a more prescient managment of traditional sources and the development of alternative sources, especially in developing countries, which are showing a sharp rise in the demand for energy

Nanocząstki węglowe jako transportery melityny do komórek glejaka IV stopnia linii U87 w modelu in vitro

Carbon nanoparticles as transporters of melittin to glioma cells in in vitro model.Substances derived from nature have natural cytotoxic properties, melittin, the main component of bee venom is one of them. It has the ability to destroy any lipid bilayer, therefore to be used in a cancer treatment it needs to be targeted. The aim is to create the drug delivery system, which would efficiently deliver the active substance to glioma cells. Carbon nanoparticles are considered to be a good agent in biomedical applications, due to their biocompatibility and small sizes. In this study five types of nanoparticles were used: pristine graphene (GN), nanographene oxide (nGO), graphite (G), nanodiamond (UDD) and hierarchical nanoporous carbons (HNCs) to target the melittin to cancer cells. The visualization of the drug delivery complexes of melittin and nanoparticles was done with transmission electron microscopy, the influence of the complexes on cell morphology and structure was pictured with scanning electron microscope. Moreover, in order to check the viability of the cells treated with melittin and the complexes of melittin and nanoparticles the PrestoBlueTM assay was done, also to specify the way of the cell death the annexin V/PI assay was carried out. The results indicate that various nanoparticles behave differently in a complex with melittin. The UDD, GN and nGO nanoparticles resulted in higher mortality than the melittin itself. Creating and applying such complexes of melittin with nanoparticles in glioma cancer treatment may be a promising solution in the therapy.Nanocząstki węglowe jako transportery melityny do komórek glejaka IV stopnia linii U87. Melityna jest jedną z naturalnie występujących substancji w przyrodzie, jest składnikiem jadu pszczelego. Jest cytotoksyczna i ma silne właściwości lityczne, które niszczą każdą błonę komórkową, co może mieć zastosowanie w zwalczaniu komórek nowotworowych, jednak aby można było ją stosować w leczeniu, wymaga dodatkowego składnika, który pokierowałby ją w odpowiednie miejsce. Celem jest stworzenie systemu kontrolowanego dostarczania leków, z wykorzystaniem nanocząstek węglowych, które mają małe rozmiary oraz są uważane za biokompatybilne. W badaniach użyto pięciu rodzajów nanocząstek: grafenu, nanotlenku grafenu, nanodiamentu, grafitu oraz hierarchicznych nanoporowatych nanocząstek. Do wizualizacji powstałego kompleksu nanocząstek z melityną użyto elektronowego mikroskopu transmisyjnego, a do sprawdzenia wpływu melityny oraz jej kompleksu z nanocząstkami na morfologię oraz strukturę komórek użyto elektronowego mikroskopu skaningowego. W celu sprawdzenia żywotności komórek poddanych działaniu melityny oraz jej kompleksów z nanocząstkami wykonano test PrestoBlueTM, a w celu specyfikacji drogi śmierci komórek test z jodkiem propidyny i aneksyną V. Wyniki wskazują, że różne rodzaje nanocząstek węglowych mogą w inny sposób oddziaływać z melityną. Kompleksy melityny z nanodiamentem, grafenem oraz nanotlenkiem grafenu spowodowały większą śmiertelność komórek niż sama melityna. Tworzenie oraz zastosowanie w praktyce kompleksów melityny z nanocząstkami węglowymi może skutkować efektywniejszym leczeniem glejaka

Wpływ melityny na żywotność i integralność błon komórkowych glejaka IV stopnia

Influence of melittin on viability and integrity of cell membrane on grade IV glioma. The grade IV glioma is one of the malignant human tumours. Today there is no effective treatment for this type of cancer. Alternative methods are sought-after in glioma treatment, and lately melittin has been found to be useful in anticancer therapy. The aim of the study was to investigate the effect of melittin on the viability and the integrity of cell membranes of the grade IV glioma cells. The U87 glioma line cells were treated of melittin in increasing concentrations (5, 10, 15, 20 and 50 µg/mL) and incubated for 24 hours. After incubation, the tests were performed in order to investigate the cell morphology, cell viability, membrane integrity and the way of cell death. The results have shown the devastating effect of melittin on the glioma cells. The melittin causes disintegration of cell membranes and induces cell death by apoptosis and less by necrosis.Wpływ melityny na żywotność i integralność błon komórkowych glejaka IV stopnia. Glejak IV stopnia jest jednym ze złośliwych nowotworów ludzkich. Do dziś nie wynaleziono skutecznego leku do walki z tym nowotworem. Melityna to jeden ze składników jadu pszczelego, który wykazuje działania antyrakowe. Celem badań było zbadanie wpływu melityny na żywotność i integralność błon komórkowych glejaka IV stopnia linii U87. Komórki glejaka IV stopnia linii U87 były traktowane roztworami melityny we wzrastającym stężeniu (5, 10, 15, 20 and 50 µg/mL) i inkubowane przed 24 godziny. Po inkubacji przeprowadzono badania w celu sprawdzenia morfologii komórek, ich żywotności, integralności błon komórkowych oraz drogę śmierci komórkowej. Wyniki wskazują na niszczący wpływ melityny na komórki glejaka. Melityna powoduje dezintegrację błon komórkowych oraz indukuje śmierć komórkową na drodze apoptozy oraz, w mniejszym stopniu, nekrozy