Integrative human and murine multi-omics: Highlighting shared biomarkers in the neuronal ceroid lipofuscinoses.

Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative disorders whose molecular mechanisms remain largely unknown. Omics approaches are among the methods that generate new information on modifying factors and molecular signatures. Moreover, omics data integration can address the need to progressively expand knowledge around the disease and pinpoint specific proteins to promote as candidate biomarkers. In this work, we integrated a total of 62 proteomic and transcriptomic datasets originating from humans and mice, employing a new approach able to define dysregulated processes across species, stages and NCL forms. Moreover, we selected a pool of differentially expressed proteins and genes as species- and form-related biomarkers of disease status/progression and evaluated local and spatial differences in most affected brain regions. Our results offer promising targets for potential new therapeutic strategies and reinforce the hypothesis of a connection between NCLs and other forms of dementia, particularly Alzheimer's disease.

PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features.

Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI2(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI2(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI2(DACH) induced cytotoxicities roughly comparable to those of oxaliplatin in three representative CRC cell lines. Moreover, it was able to trigger cell apoptosis, to an extent even better than cisplatin and oxaliplatin. Overall, a rather promising picture emerges for this novel Pt drug that merits, in our opinion, a deeper and more extensive preclinical evaluation.

Candidate biomarkers for mosquito age-grading identified by label-free quantitative analysis of protein expression in Aedes albopictus females.

We applied a "shotgun" approach based on nanoliquid chromatography-high resolution mass spectrometry associated to label free quantification (LFQ) to identify proteins varying with age, independently from the physiological state, in Aedes albopictus, a mosquito species which in the last decades invaded temperate regions in North America and Europe, creating concerns for associated high nuisance and risk of arbovirus transmission. The combined "shotgun" and LFQ approach was shown to be highly suitable to simultaneously compare several biological samples, as needed in a study aimed to analyze different age-groups and physiological states of adult mosquito females. The results obtained represent the first wide-scale analysis of protein expression in Ae. albopictus females: >1000 and 665 proteins were identified from few micrograms of crude protein extracts of mosquito heads and thoraxes, respectively. Six of these proteins were shown to significantly vary from 2- to 16-day-old females, independently from their physiological state (i.e. virgin, mated, host-seeking, blood-fed, and gravid). BIOLOGICAL SIGNIFICANCE: Mosquito-borne diseases, such as malaria, dengue and other arboviroses, are a persistent cause of global mortality and morbidity, affecting hundreds of thousands of people. Billions of people living in tropical areas are at risk of being bitten every day by an infective mosquito female and the spread of tropical species such as Aedes albopictus to temperate areas is creating alarm in the northern hemisphere. Mosquito longevity is a critical factor affecting mosquito-borne pathogen transmission cycles and the mosquito capacity to transmit pathogens. However, large scale analyses of the age structure of mosquito field populations is hampered by the lack of optimal age-grading approaches. Our findings open new perspectives for the development of reliable, simple and cheap protein-based assays to age-grade Ae. albopictus females and, most likely, other mosquito species of higher medical relevance, such as the main dengue vector, Aedes aegypti, and the major Afrotropical malaria vectors. These assays would greatly contribute to epidemiological studies aimed at defining the actual vectorial capacity of a given mosquito species. Moreover, they would be very valuable in assessing the effectiveness of mosquito control interventions based on the relative ratio between young and old individuals before and after the intervention.

Interactions of selected gold(III) complexes with DNA G quadruplexes.

The interactions of three representative gold(III) complexes with human telomeric DNA sequences were analysed using a variety of biophysical methods, including DNA melting, circular dichroism, SPR and ESI MS; remarkable interactions were highlighted for all tested complexes, although they were associated to significantly different binding profiles. The most interesting compound was Auoxo6, a dinuclear gold(III) complex, which beyond manifesting a conspicuous binding affinity for the G-quadruplex conformation, turned out to be very effective in inducing a non-canonical secondary structure. These findings may clear the way for novel biological and pharmacological applications of this class of metal compounds.

Top-down sequencing of Apis dorsata apamin by MALDI-TOF MS and evidence of its inactivity against microorganisms.

Apis mellifera venom is one of the best characterized venoms among Hymenoptera, yet relatively little is known about venom belonging to other species in the genus Apis. Melittin, one of the most important bioactive peptides, has been isolated and characterized in A. mellifera, Apis cerana, Apis dorsata and Apis florea, while apamin has been only characterized in A. mellifera and A. cerana. At present, no information is available about the sequence of A. dorsata apamin. Moreover, while the antiseptic properties of melittin and MCD peptides are well documented, the antimicrobial activity of apamin has never been tested. In the present study, we isolated and characterized apamin from the venom of the giant honeybee A. dorsata. We tested the activity of apamin against bacteria and yeasts in a microbiological assay to gain a more complete understanding of the antimicrobial competence of the medium molecular weight venom fraction. We show that A. dorsata apamin toxin has the same primary sequence as apamin in A. mellifera and A. cerana, yet with a different C-terminal amidation. We did not find any antiseptic activity of apamin against any of the tested microorganisms. We discuss the evolutionary processes connected to the ecological context of venom use that drove the generation of Apis venom complexity.