Age-related changes in human periosteal derived stem cells: a matter for effective bone regeneration strategies

Possible age-related changes in Mesenchymal Stem Cells (MSCs) are of great inter- est in view of their use for regenerative medicine approaches also in the elderly. Con- sidering the primary role of periosteum in bone biology and to acquire data for a cell- based therapy stimulating graft osseointegration, we tried to identify specific aging markers or pattern of expression in human periosteal precursor cells (PDPCs). To this aim periosteal tissue was obtained from differently aged healthy subjects, gender matched with a mean age of 16, 28, 63 and 92 years. Immunohistochemical detection of Ki67 and p53, Nitric Oxide (NO) production and qRT- PCR of a selected gene pan- el for early osteoblastic differentiation (bmp2 and runx2) and bone remodelling (IL-6, RANKL and OPG) were evaluated. Our data evidenced that both Ki67 and p53 rep- resent striking markers of cell-cycle arrest in these cells and that their expression cor- relates with NO production. In addition, age affects genes involved in bone remodel- ling, with a significant increase in IL-6 mRNA expression as well as in RANKL/OPG ratio. As far as NO release is concerned, our data showed higher levels in PDPCs iso- lated from the elderly and a good correlation with the immunohistochemical analysis Moreover, mathematical modelling, in silico simulations and biochemical experiments were combined to investigate about possible underlying quantitative correlations. A clear one-term exponential relationship emerged from a comparison of involved marker trends against age of donors concerning measured NO concentration / Ki67 ratio. This analytical approach confirmed Ki67 as a senescence marker to be focused on. We believe that this study, taking into account age-related changes in human PDPCs, opens up new regenerative medicine strategies for aged bone and/or bone metabolic diseases

Analysis of tight junctions in placentas affected by chorioamnionitis: in vivo and in vitro analysis

The human placenta and fetal membranes provide a barrier regulating the transfer of materials between the mother and the developing fetus throughout gestation. Chorioamnionitis is an important risk factor for preterm delivery that is associated with high perinatal morbidity and mortality. Chorioamnionitis is the term applied to infections of the placenta and membranes resulting in high concentrations of IL- 1beta, IL-6, IL-8 and TGF-beta in the amniotic fluid (D’Alquen et al., 2005). With progression of inflammation, immune cells penetrate blood vessels and infiltrate the umbilical cord, resulting in funisitis (Romero and Mazor, 1988). In normal conditions the two important physical entities in endothelial/epithelial paracellular clefts are adherens junctions and tight junctions. Tight junction governs the paracellular movement of water, solutes and immune cells, through the intercellular space creating a boundary between the apical and basolateral sides of cellular barriers (Gruenheid and Finlay, 2003). We have evaluated the localization of tight junctions studying the Zonula Occludens-1 (ZO-1) and Occludin expressions as well as the localization of adherent junctions, testing the expression of VE-cadherin and beta-catenin in placentas from normal gestations, from preterm idiopathic deliveries and from chorioamnionitis by immunohistochemistry. In addition, we have evaluated the mRNAs by real time PCR, the protein levels of these molecules by Western blot analysis in placental tissues, and to better clarify the action of some cytokines on occludin we performed in vitro analysis of HUVEC cultures. Our more striking result is the decrease of occludin expression in placentas from chorioamnionitis and an evident action of the cytokines on this molecule

Functional MRI cortical activations from unilateral tactile-taste stimulations of the tongue

Functional magnetic resonance imaging (fMRI) was used for revealing activations in the human brain by lateralized tactile-gustatory stimulations of the tongue. Salt, a basic taste stimulus, and water, now recognized as an independent taste modality, were applied to eitherhemitongues with pads similar to the taste strips test for the clinical psychophysical evaluation of taste. With both stimuli, the observed cortical patterns of activations could be attributed to a combined somatosensory and gustatory stimulation of the tongue, with no significant differences between salt and water. Stimulation of each hemitongue evoked a bilateral activation of the anterior insula-frontal operculum, ascribable to the gustatory component of the stimulation, and a bilateral activation of the inferior part of the postcentral gyrus, ascribable to the tactile component of the stimulation. The results are in line with the notion that the representationof the tongue in the cerebral hemispheres in both the touch and the taste modalities is bilateral. Clinical and brain stimulation findings indicate that this bilaterality depends primarily on a partial crossing of the afferent pathways, perhaps with a predominance of the crossed pathway in the touch modality and the uncrossed pathway in the taste modality. Previous evidence suggests that the corpus callosum is not indispensible for this bilateral representation, but can contribute to it by interhemispheric transfer of information in both modalities

Human Periosteal Derived Stem Cell Potential: The Impact of age

In the repair of skeletal defects one of the major obstacles still remains an efficient vascularization of engineered scaffolds. We have examined the ability of insulin growth factor-1, alone or in association with vascular endothelial growth factor, to modulate the osteoblastic or endothelial commitment of periosteum-derived progenitor cells (PDPCs) and skin-derived multipotent stromal cells (S-MSCs). A selected gene panel for endothelial and osteoblastic differentiation as well as genes that can affect MAPK and PI3K/AKT signaling pathways were investigated. Moreover, gene expression profile of Sox2, Oct4, and Nanog transcription factors was assessed. Our results showed that under growth factor stimulation PDPCs are induced toward an osteoblastic differentiation, while S-MSCs seem to move along an endothelial phenotype. This different commitment seems to be linked to a diverse MAPK or PI3K/AKT signaling pathway activation. The analysis of genes for stemness evidenced that at least in PDPCs multipotency and differentiation could coexist. These results open interesting perspective for the development of innovative bone tissue engineering approaches based on a good network of angiogenesis and osteogenesis processes

CT and MRI diagnosis of silent sinus syndrome

PURPOSE: The purpose of this study was to determine computed tomography (CT) and magnetic resonance (MR) findings of silent sinus syndrome (SSS) - a rare clinical entity with the constellation of progressive enophthalmos and hypoglobus, facial asymmetry and possible diplopia - due to otherwise asymptomatic maxillary sinus disease. MATERIALS AND METHODS: We reviewed the pre- and postoperative CT and MR images of six patients with a definitive diagnosis of SSS and compared the radiological and clinical findings with those reported in the literature. RESULTS: The CT and MR studies demonstrated in all cases the most characteristic imaging features of SSS reported in the literature. CONCLUSIONS: Both CT and MR imaging enable a diagnosis of SSS to be made, but CT provides a better depiction of all features of SSS necessary for diagnosis and differentiation from other sinus conditions, even in patients without a clinical suspicion of SSS

Increased Prevalence of Headaches and Migraine in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: Insights from an Italian Cohort Study

Background: Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are inflammatory diseases with shared genetic backgrounds and clinical comorbidities. Headache, a common global health issue, affects over 50% of adults and encompasses various types, including migraine, tension-type, and cluster headaches. Migraine, the most prevalent, recurrent, and disabling type, is often associated with other medical conditions such as depression, epilepsy, and psoriasis, but little is known about the relationship between autoimmune disease and the risk of migraine. Methods: A cross-sectional study was conducted from July to November 2022, enrolling 286 participants, including 216 with PsA, 70 with axSpA, and 87 healthy controls. Results: Headache prevalence was significantly higher in the PsA (39.81%) and axSpA (45.71%) patients compared to the healthy controls. The prevalence of migraine without aura was also significantly higher in both the PsA (18.52%) and axSpA (28.57%) groups compared to the healthy controls. Conclusions: These findings underscore the high burden of headache and migraine in PsA and axSpA participants, highlighting the need for improved management and treatment strategies for these patients