Fiche de lecture. Xavier-Laurent Petit, Itawapa

Note de lectureInternational audienc

Fiche de lecture. Françoise du Chaxel, La Terre qui ne voulait plus tourner.

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Fiche de lecture. Jacques Cassabois La colère des hérissons

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Targeting ddx3x helicase activity with ba103 shows promising therapeutic effects in preclinical glioblastoma models

DDX3X is an ATP-dependent RNA helicase that has recently attracted interest for its involvement in viral replication and oncogenic progression. Starting from hit compounds previously identified by our group, we have designed and synthesized a new series of DDX3X inhibitors that effectively blocked its helicase activity. These new compounds were able to inhibit the proliferation of cell lines from different cancer types, also in DDX3X low-expressing cancer cell lines. According to the absorption, distribution, metabolism, elimination properties, and antitumoral activity, compound BA103 was chosen to be further investigated in glioblastoma models. BA103 determined a significant reduction in the proliferation and migration of U87 and U251 cells, downregulating the oncogenic protein β-catenin. An in vivo evaluation demonstrated that BA103 was able to reach the brain and reduce the tumor growth in xenograft and orthotopic models without evident side effects. This study represents the first demonstration that DDX3X-targeted small molecules are feasible and promising drugs also in glioblastoma

L'ambiente Costiero Ionico Lucano (Mt): un valore culturale e paesaggistico da salvaguardare

none7noneSIMEONI U.; TESSARI U.; TRIVISANI A.; CORBAU C.; RODELLA I.; TRIVISANI V.; GIANNINI G.Simeoni, U.; Tessari, U.; Trivisani, A.; Corbau, C.; Rodella, I.; Trivisani, V.; Giannini, G

Progress towards adjuvant development: focus on antiviral therapy

In recent decades, vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of one or more adjuvants represents the key to enhance the response of the immune signal to the antigen, thus accelerating and increasing the duration and the potency of the protective effect. Their use is of particular importance for vulnerable populations, such as the elderly or immunocompromised people. Despite their importance, only in the last forty years has the search for novel adjuvants increased, with the discovery of novel classes of immune potentiators and immunomodulators. Due to the complexity of the cascades involved in immune signal activation, their mechanism of action remains poorly understood, even if significant discovery has been recently made thanks to recombinant technology and metabolomics. This review focuses on the classes of adjuvants under research, recent mechanism of action studies, as well as nanodelivery systems and novel classes of adjuvants that can be chemically manipulated to create novel small molecule adjuvants

La ‘diabolica’ colpa di Edipo. Rinarrare il mito oggi fra letteratura e cinema: dal romanzo noir ad Angel Heart di Alan Parker.

Sophocles’ Oedipus the King is considered the prototype of modern detective stories. Alain Robbe-Grillet, in his novel Les Gommes, transforms the story of Oedipus into a typical noir and William Hjortsberg uses it as a hypotext for his ‘demonic’ crime novel Falling Angel. On this book Alan Parker based his movie Angel Heart, where the main elements of the myth of Oedipus are rendered through original solutions, closely linked to the peculiarities of film language

Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases

Removal of ribonucleotides (rNMPs) incorporated into the genome by the ribonucleotide excision repair (RER) is essential to avoid genetic instability. In eukaryotes, the RNaseH2 is the only known enzyme able to incise 5' of the rNMP, starting the RER process, which is subsequently carried out by replicative DNA polymerases (Pols) δ or ε, together with Flap endonuclease 1 (Fen-1) and DNA ligase 1. Here, we show that the DEAD-box RNA helicase DDX3X has RNaseH2-like activity and can support fully reconstituted in vitro RER reactions, not only with Pol δ but also with the repair Pols β and λ. Silencing of DDX3X causes accumulation of rNMPs in the cellular genome. These results support the existence of alternative RER pathways conferring high flexibility to human cells in responding to the threat posed by rNMPs incorporation