Emilio Cirri

Peripheral nervous system (PNS) ageing is marked by structural and functional decline, yet it remains unclear whether ageing constitutes a distinct biological programme or reflects a chronic injury-like state. To address this, we performed an unbiased, comparative molecular analysis of PNS ageing, neuroprotective dietary restriction (DR), and nerve injury. We conducted transcriptomic and proteomic profiling of peripheral nerves from young, old and geriatric mice fed ad libitum or subjected to long-term DR, and proteomics of nerves collected at multiple time points following injury. Age-associated molecular changes followed both linear and non-linear trajectories, and DR partially attenuated these ageing-related alterations. Notably, ageing-and injury-induced proteomic signatures showed considerable similarities, supporting the concept that an aged nerve resembles an injured nerve. Together, our study provides the most comprehensive molecular resource of PNS changes during ageing, DR, and injury, enabling the definition of key molecular signatures underlying PNS physiology. All datasets are integrated into the “PNS-omics Viewer”, a Shiny web application designed to facilitate data mining of the herein presented datasets ( tba ).

In this study we looked for the main protein pathway regulators which were responsible for the therapeutic impact on colon cancers when combining magnetic hyperthermia with the chemotherapeutic agent 5-fluorouracil (5FU). To this end, chitosan-coated magnetic nanoparticles (MNP) functionalized with 5FU were intratumorally injected into subcutaneous human colon cancer xenografts (HT-29) in mice and exposed to an alternating magnetic field. A decreased tumor growth was found particularly for the combined thermo-chemotherapy vs. the corresponding monotherapies. By using computational analysis of the tumor proteome, we found upregulated functional pathway categories termed “cellular stress and injury”, “intracellular second messenger and nuclear receptor signaling”, “immune responses”, and “growth proliferation and development”. We predict TGF-beta, and other mediators, as important upstream regulators. In conclusion, our findings show that the combined thermo-chemotherapy induces thrombogenic collagen fibers which are able to impair tumor nutrient supply. Further on, we associate several responses to the recognition of damage associated molecular patterns (DAMPs) by phagocytic cells, which immigrate into the tumor area. The activation of some pathways associated with cell survival implies the necessity to conduct multiple therapy sessions in connection with a corresponding monitoring, which could possibly be performed on the base of the identified protein regulators.