This present work characterizes the fatty acid constituents of the lipid fraction of royal jelly. Among the organic acids found after fractionation by thin layer chromatography of the corresponding methyl esters, the following compounds were identified by combined GC-MS: saturated and unsaturated linear fatty acids, saturated and unsaturated linear and branched dicarboxylic acids, mono-and dihydroxy acids. The most common characteristic of the organic acids was that most contained 8 or 10 carbon atoms, whether saturated or unsaturated, linear or branched
Our laboratory has pursued the generation of cancer-specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor-Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off-target and off-tumor infections and preservation of the full complement of unmodified viral genes. These oHSVs are “fully virulent in their target cancer cells”. The 3rd generation retargeted oHSVs carry two distinct retargeting moieties, which enable infection of a producer cell line and of the target cancer cells, respectively. They can be propagated in an ad hoc Vero cell derivative at about tenfold higher yields than 1st generation recombinants, and more effectively replicate in human cancer cell lines. The R-335 and R-337 prototypes were armed with murine IL-12. Intratumorally-administered R-337 conferred almost complete protection from LLC-1-HER2 primary tumors, unleashed the tumor microenvironment immunosuppression, synergized with the checkpoint blockade and conferred long-term vaccination against distant challenge tumors. In summary, the problem intrinsic to the propagation of retargeted oHSVs—which strictly require cells positive for targeted receptors—was solved in 3rd generation viruses. They are effective as immunotherapeutic agents against primary tumors and as antigen-agnostic vaccines.
The studies of insects from archaeological contexts can provide an important supplement of information to reconstruct past events, climate and environments. Furthermore, the list of the species present in an area in the past allows the reconstruction of the entomofauna on that area at that time, that can be different from the nowadays condition, providing information about biodiversity changes. In this work, the results of a funerary archaeoentomological study on samples collected from mummified corpses discovered during the restoration of the crypt of the Sant’Antonio Abate Cathedral of Castelsardo (Sardinia, Italy) are reported. The majority of the sampled specimens were Diptera puparia, whereas only few Lepidoptera cocoons and some Coleoptera fragments were isolated. Among Diptera, Calliphoridae puparia were identified as Phormia regina (Meigen, 1826) and Calliphora vicina, (Robineau-Desvoidy, 1830) both species typical of the first colonization waves of exposed bodies. Three puparia fragments were also identified as belonging to a Sarcophaga Meigen, 1826, species (Sarcophagidae). Several Muscidae puparia of the species Hydrotaea capensis (Weidmermann, 1818), a late colonizer of bodies, and typical of buried bodies were also collected. The few moth (Lepidoptera) cocoons were identified as belonging to the family Tineidae. This family comprises species feeding on dry tissues and hair typical of the later phases of the human decomposition. Among Coleoptera a single specimen in the family Histeridae, Saprinus semistriatus (Scriba, 1790) and a single elytra, potentially of a species in the family Tenebrionidae, were also collected. Overall, the samples collected indicated an initial colonization of the bodies in an exposed context, mainly in a warm season. This research allows the finding of elements indicating the presence, at least in the past, of P. regina in Sardinia. This species at the moment seems extinct from Sardinia while it is quite common in the continent.
Flies and beetles are the main components of the entomofauna colonizing a body after death. Following the recognition of constant and predictable colonization patterns and the knowledge about the dependence of the insect development to temperature, a new discipline, forensic entomology, has provided information useful to reconstruct criminal events. Funerary archaeoentomology has also applied the same rationale in archaeological contexts. Puparia represent a large fraction of the insect remains that can be found associated with a cadaver, especially when the body is mummified or in the advanced stages of decomposition. Puparium identification is still a problematic topic due to the lack of identification keys and, in several cases, a lack of diagnostic feature descriptions. Here, we focus the attention on some Hydrotaea Robineau-Desvoidy (Diptera, Muscidae) puparia from forensic and archaeological contexts. Puparia of Hydrotaea capensis (Wiedemann), Hydrotaea ignava (Harris), Hydrotaea aenescens (Wiedemann), Hydrotaea similis Meade, Hydrotaea pilipes Stein, and Hydrotaea dentipes (Fabricius) are here detailed and illustrated. Posterior spiracles, anal plate, and intersegmental spines have been considered as good diagnostic characters for the identification of these puparia.
The efficient treatment of hematological malignancies as Acute Myeloid Leukemia, myelofibrosis and Chronic Myeloid Leukemia, requires the elimination of cancer-initiating cells and the prevention of disease relapse through targeting pathways that stimulate generation and maintenance of these cells. In mammals, inhibition of Smoothened, the key mediator of the Hedgehog signaling pathway, reduces Chronic Myeloid Leukemia progression and propagation. These findings make Smo a candidate target to inhibit maintenance of leukemia-initiating cells. In Drosophila melanogaster the same pathway maintains the hematopoietic precursor cells of the lymph gland, the hematopoietic organ that develops in the larva. Using Drosophila as an in vivo model, we investigated the mode of action of PF-04449913, a small-molecule inhibitor of the human Smo protein. Drosophila larvae fed with PF-04449913 showed traits of altered hematopoietic homeostasis. These include the development of melanotic nodules, increase of circulating hemocytes, the size increase of the lymph gland and accelerated differentiation of blood cells likely due to the exit of multi-potent precursors from quiescence. Importantly, the Smo inhibition can lead to the complete loss of hematopoietic precursors. We conclude that PF-04449913 inhibits Drosophila Smo blocking the Hh signaling pathway and causing the loss of hematopoietic precursor cells. Interestingly, this is the effect expected in patients treated with PF-04449913: number decrease of cancer initiating cells in the bone marrow to reduce the risk of leukemia relapse. Altogether our results indicate that Drosophila comprises a model system for the in vivo study of molecules that target evolutionary conserved pathways implicated in human hematological malignancies.
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