How Widespread Are the “Young” Neurons of the Mammalian Brain?

After the discovery of adult neurogenesis (stem cell-driven production of new neuronal elements), it is conceivable to find young, undifferentiated neurons mixed with mature neurons in the neural networks of the adult mammalian brain. This “canonical” neurogenesis is restricted to small stem cell niches persisting from embryonic germinal layers, yet, the genesis of new neurons has also been reported in various parenchymal brain regions. Whichever the process involved, several populations of “young” neurons can be found at different locations of the brain. Across the years, further complexity emerged: (i) molecules of immaturity can also be expressed by non-dividing cells born during embryogenesis, then maintaining immature features later on; (ii) remarkable interspecies differences exist concerning the types, location, amount of undifferentiated neurons; (iii) re-expression of immaturity can occur in aging (dematuration). These twists are introducing a somewhat different definition of neurogenesis than normally assumed, in which our knowledge of the “young” neurons is less sharp. In this emerging complexity, there is a need for complete mapping of the different “types” of young neurons, considering their role in postnatal development, plasticity, functioning, and interspecies differences. Several important aspects are at stake: the possible role(s) that the young neurons may play in maintaining brain efficiency and in prevention/repair of neurological disorders; nonetheless, the correct translation of results obtained from laboratory rodents. Hence, the open question is: how many types of undifferentiated neurons do exist in the brain, and how widespread are they

Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment

Abstract Advanced therapies which combine cells with biomaterial-based carriers are recognized as an emerging and powerful method to treat challenging diseases, such as spinal cord injury (SCI). By enhancing transplanted cell survival and grafting, biomimetic hydrogels can be properly engineered to encapsulate cells and locate them at the injured site in a minimally invasive way. In this work, chitosan (CS) based hydrogels were developed to host mesenchymal stem cells (MSCs), since their paracrine action can therapeutically enhance the SC regeneration, limiting the formation of a glial scar and reducing cell death at the injured site. An injectable and highly permeable CS-based hydrogel was fabricated having a rapid gelation upon temperature increase from 0 to 37 °C. CS was selected as former material both for its high biocompatibility that guarantees the proper environment for MSCs survival and for its ability to provide anti-inflammatory and anti-oxidant cues. MSCs were mixed with the hydrogel solution prior to gelation. MSC viability was not affected by the CS hydrogel and encapsulated MSCs were able to release MSC-vesicles as well as to maintain their anti-oxidant features. Finally, preliminary in vivo tests on SCI mice revealed good handling of the CS solution loading MSCs during implantation and high encapsulated MSCs survival after 7 days

Effects of vanadyl complexes with acetylacetonate derivatives on non-tumor and tumor cell lines

Vanadium has a good therapeutic potential, as several biological effects, but few side effects, have been demonstrated. Evidence suggests that vanadium compounds could represent a new class of non-platinum, metal antitumor agents. In the present study, we aimed to characterize the antiproliferative activities of fluorescent vanadyl complexes with acetylacetonate derivates bearing asymmetric substitutions on the β-dicarbonyl moiety on different cell lines. The effects of fluorescent vanadyl complexes on proliferation and cell cycle modulation in different cell lines were detected by ATP content using the CellTiter-Glo Luminescent Assay and flow cytometry, respectively. Western blotting was performed to assess the modulation of mitogen-activated protein kinases (MAPKs) and relevant proteins. Confocal microscopy revealed that complexes were mainly localized in the cytoplasm, with a diffuse distribution, as in podocyte or a more aggregate conformation, as in the other cell lines. The effects of complexes on cell cycle were studied by cytofluorimetry and Western blot analysis, suggesting that the inhibition of proliferation could be correlated with a block in the G2/M phase of cell cycle and an increase in cdc2 phosphorylation. Complexes modulated mitogen-activated protein kinases (MAPKs) activation in a cell-dependent manner, but MAPK modulation can only partly explain the antiproliferative activity of these complexes. All together our results demonstrate that antiproliferative effects mediated by these compounds are cell type-dependent and involve the cdc2 and MAPKs pathway

Molecular Aspects of the Interaction with Gram-Negative and Gram-Positive Bacteria of Hydrothermal Carbon Nanoparticles Associated with Bac8c2,5Leu Antimicrobial Peptide

Molecular Aspects of the Interaction with Gram-Negative and Gram- Positive Bacteria of Hydrothermal Carbon Nanoparticles Associated with Bac8c2,5Leu Antimicrobial Peptide Giulia Barzan,⊥ Ida Kokalari,⊥ Giacomo Gariglio, Elena Ghibaudi, Marc Devocelle, Marco P. Monopoli, Alessio Sacco, Angelo Greco, Andrea M. Giovannozzi, Andrea M. Rossi, and Ivana Fenoglio* Cite This: https://doi.org/10.1021/acsomega.2c00305 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: Antimicrobial peptides (AMPs) are widely studied as therapeutic agents due to their broad-spectrum efficacy against infections. However, their clinical use is hampered by the low in vivo bioavailability and systemic toxicity. Such limitations might be overcome by using appropriate drug delivery systems. Here, the preparation of a drug delivery system (DDS) by physical conjugation of an arginine-rich peptide and hydrothermal carbon nanoparticles (CNPs) has been explored, and its antimicrobial efficacy against Eschericia coli (E. coli) and Staphylococcus aureus investigated in comparison with the unloaded carrier and the free peptide. The mechanism of interaction between CNPs and the bacteria was investigated by scanning electron microscopy and a combined dielectrophoresis−Raman spectroscopy method for real- time analysis. In view of a possible systemic administration, the effect of proteins on the stability of the DDS was investigated by using albumin as a model protein. The peptide was bounded electrostatically to the CNPs surface, establishing an equilibrium modulated by pH and albumin. The DDS exhibited antimicrobial activity toward the two bacterial strains, albeit lower as compared to the free peptide. The decrease in effectiveness toward E. coli was likely due to the rapid formation of a particle-induced extracellular matrix. The present results are relevant for the future development of hydrothermal CNPs as drug delivery agents of AMP

Psychopathology of addiction: May a SCL-90-based five dimensions structure be applied irrespectively of the involved drug?

BACKGROUND: We previously found a five cluster of psychological symptoms in heroin use disorder (HUD) patients: ‘worthlessness-being trapped’, ‘somatic-symptoms’, ‘sensitivity-psychoticism’, ‘panic-anxiety’, and ‘violence-suicide’. We demonstrated that this aggregation is independent of the chosen treatment, of intoxication status and of the presence of psychiatric problems. METHODS: 2314 Subjects, with alcohol, heroin or cocaine dependence were assigned to one of the five clusters. Differences between patients dependent on alcohol, heroin and cocaine in the frequency of the five clusters and in their severity were analysed. The association between the secondary abuse of alcohol and cocaine and the five clusters was also considered in the subsample of HUD patients. RESULTS: We confirmed a positive association of the ‘somatic symptoms’ dimension with the condition of heroin versus cocaine dependence and of the ‘sensitivity-psychoticism’ dimension with the condition of alcohol versus heroin dependence. ‘Somatic symptoms’ and ‘panic anxiety’ successfully discriminated between patients as being alcohol, heroin or cocaine dependents. Looking at the subsample of heroin dependents, no significant differences were observed. CONCLUSIONS: The available evidence coming from our results, taken as a whole, seems to support the extension of the psychopathological structure previously observed in opioid addicts to the population of alcohol and cocaine dependents

Psychopathological symptoms of patients with heroin addiction entering opioid agonist or therapeutic community treatment.

The relationship between substance use disorders and psychiatric pathology is still an open question. The main aim of the present study was to verify whether the five psychopathological dimensions identified through the SCL-90 tool in a previous study carried out on patients with heroin addiction entering an outpatient opioid agonist treatment (OAT) were also observable in those entering a residential treatment community (TC). Further aims were to look at differences in the psychopathological profiles of patients entering a TC versus an OAT treatment and at the correlation between gender and the observed psychopathology.A confirmatory factor analysis was performed on the results of SCL-90 filled by 1,195 patients with heroin dependence entering TC treatment. It replicates the extraction method previously used on 1,055 OAT patients with heroin addiction by using a principal component factor analysis (PCA). The association between the kind of treatment received (TC or OAT), gender, and the psychopathological dimensions was assessed through logistic regression and general linear model (GLM) analysis.The PCA carried out on the SCL-90 results of patients entering a TC yielded a five-factor solution, confirming the same dimensions observed in patients entering an OAT: 'worthlessness and being trapped', 'somatization', 'sensitivity-psychoticism', 'panic anxiety', and 'violence-suicide'. The logistic regression analysis showed a statistically significant association between 'somatization' and 'violence-suicide' severity score and OAT. GLM analysis showed that psychopathological factorial scores for 'worthlessness-being trapped', 'somatic symptoms', and 'panic anxiety' dimensions were more severe in OAT vs TC male patients and in TC vs OAT female ones. 'Violence suicide' followed the same severity pattern for males, but did not differ in TC vs OAT females, while 'sensitivity-psychoticism' did not differ in OAT vs TC patients. The five dimensions did not differ in OAT males vs females.Our research appears to confirm the existence of a specific aggregation of psychological/psychiatric features within the category of individuals with heroin addiction. It also shows a correlation between the dominant psychopathological subgroup and the assignment to TC versus OAT. Further research is needed to clarify the differences between the five psychopathological subgroups and their determinants