Showing papers by "Elena Mele published in 2022"

Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis

Abstract: The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis.

Neuroinflammation: molecular mechanisms and therapeutic perspectives.

Abstract: BACKGROUND Neuroinflammation is a key component in the etiopathogenesis of neurological diseases and brain aging. This process involves the brain immune system that modulates synaptic functions and protects neurons from infection or damage. Hence, the knowledge of neuroinflammation related-pathways and modulation by drugs or natural compounds is functional to the development of therapeutic strategies aimed at preserving, maintaining and restoring brain health. OBJECTIVE This review article summarizes the basics in neuroinflammation and related signaling pathways, the success of dietary intervention in clinical practice and the possible development of RNA-based strategies for the treatment of neurological diseases. METHODS Pubmed search (2012-2022); keywords: neuroinflammation and molecular mechanisms in combination with diet, miRNA and non-coding RNA. RESULTS Glial cells play a crucial role in neuroinflammation, but several pathways can be activated in response to different inflammatory stimuli, inducing cell death by apoptosis, pyroptosis or necroptosis. Dietary intervention has immunomodulatory effects and could limit the inflammatory process induced by microglia and astrocytes. Thus by ihibiting neuroinflammation and improving the symptoms of a variety of neurological diseases, diet exerts pleiotropic neuroprotective effects independently from the spectrum of pathophysiological mechanisms underlying the specific disorder. Furthermore, data from animal models revealed that altered expression of specific non-coding RNAs, in particular microRNAs, contributes to neuroinflammatory diseases; consequently, RNA-based strategies may be promising to alleviate the consequences of neuroinflammation. CONCLUSION Further studies are needed to identify the molecular pathways and the new pharmacological targets in neuroinflammation to lay the basis for more effective and selective therapies to be applied, in parallel to dietary intervention, in the treatment of neuroinflammation-based diseases.

Improving the Seismic Response of Tall Buildings: From Diagrid to Megastructures and Mega-Subcontrol Systems

Abstract: Diagrid structures, widely used for the tall buildings of the third millennium, are characterized by a very effective behaviour in the elastic field due to the grid triangulation. In particular, under horizontal actions, axial forces and deformations mainly arise in the structural members of the diagrid, thus resulting in the reduction of the shear lag effect and racking deformations. The response to incremental horizontal actions beyond the plastic threshold, however, shows a poor plastic redistribution capacity, with consequent low values of global ductility, in spite of a significant design overstrength. In this paper, it is proposed to exploit the high elastic efficiency of the diagrid type and use a vibration control system, based on mass damping mechanism with large mass ratios, to reduce a priori the inelastic demands due to seismic actions. Starting from the analysis of the seismic behavior of archetype diagrid buildings, a case study is selected to assess the effectiveness of the proposed motion-based design approach. For this purpose, the diagrid is first transformed into a megastructure (MS) configuration by densifying the diagonal elements at the most stressed corner areas and transfer floors, suitably chosen. Then, the exterior mega-frame is detached from interior sub-structures, thus allowing for a relative motion between the two structural portions according to a “mega-sub-structure control system” (MSCS), which activates the mass damping mechanism. Time-history analyses carried out on simplified lumped-mass models confirm the effectiveness of the proposed strategy in reducing the seismic response. Finally, the practical feasibility of the MSCS and engineering solutions for the relevant structural organization are discussed.