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Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown. In this study, PACAP/VIP levels were assessed in the brain of GFAP-IL6 mice. In addition, we utilised bi-genic GFAP-IL6 mice carrying the human sgp130-Fc transgene (termed GFAP-IL6/sgp130Fc mice) to determine whether trans-signalling inhibition rescued PACAP/VIP changes in the CNS. Transcripts and protein levels of PACAP and VIP, as well as their receptors PAC1, VPAC1 and VPAC2, were significantly increased in the cerebrum and cerebellum of GFAP-IL6 mice vs. wild type (WT) littermates. These results were paralleled by a robust activation of the JAK/STAT3, NF-κB and ERK1/2MAPK pathways in GFAP-IL6 mice. In contrast, co-expression of sgp130Fc in GFAP-IL6/sgp130Fc mice reduced VIP expression and activation of STAT3 and NF-κB pathways, but it failed to rescue PACAP, PACAP/VIP receptors and Erk1/2MAPK phosphorylation. We conclude that forced expression of IL-6 in astrocytes induces the activation of the PACAP/VIP neuropeptide system in the brain, which is only partly modulated upon IL-6 trans-signalling inhibition. Increased expression of PACAP/VIP neuropeptides and receptors may represent a homeostatic response of the CNS to an uncontrolled IL-6 synthesis and its neuroinflammatory consequences. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong neuroinflammatory component. Current treatments principally target the immune system but fail to preserve long‐term myelin health and do not prevent neurological decline. Studies over the past two decades have shown that the structurally related neuropeptides VIP and PACAP (vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide, respectively) exhibit pronounced anti‐inflammatory activities and reduce clinical symptoms in MS disease models, largely via actions on their bivalent VIP receptor type 1 and 2. Here, using the cuprizone demyelination model, we demonstrate that PACAP and VIP, and strikingly the PACAP‐selective receptor PAC1 agonist maxadilan, prevented locomotor deficits in the horizontal ladder and open field tests. Moreover, only PACAP and maxadilan were able to prevent myelin deterioration, as assessed by a reduction in the expression of the myelin markers proteolipid protein 1, oligodendrocyte transcription factor 2, quaking‐7 (APC) and Luxol Fast Blue staining. Furthermore, PACAP and maxadilan (but not VIP), prevented striatal synaptic loss and diminished astrocyte and microglial activation in the corpus callosum of cuprizone‐fed mice. In vitro, PACAP or maxadilan prevented lipopolysaccharide (LPS)‐induced polarisation of primary astrocytes at 12–24 h, an effect that was not seen with maxadilan in LPS‐stimulated microglia. Taken together, our data demonstrates for the first time that PAC1 agonists provide distinctive protective effects against white matter deterioration, neuroinflammation and consequent locomotor dysfunctions in the cuprizone model. The results indicate that targeting the PAC1 receptor may provide a path to treat myelin‐related diseases in humans. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing–remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors' levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and/or other demyelinating disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to analyze the body composition and somatotype of professional soccer players, investigating variations across categories and playing positions. METHODS: An observational, cross-sectional, and analytical study was conducted with 51 male professional soccer players in the U-19 and U-20 categories. Data about sex, age, height, and weight were collected between March and May 2023. Body composition analysis utilized the ISAK protocol for the restricted profile, while somatotype categorization employed the Heath and Carter formula. Statistical analysis was performed using IBM SPSS Statistics V.26, which involved the application of Mann-Whitney and Kruskal-Wallis tests to discern differences in body composition variables and proportionality based on categories and playing positions. The Dunn test further identified specific positions exhibiting significant differences. RESULTS: The study encompassed 51 players, highlighting meaningful differences in body composition. The average body mass in kg was 75.8 (±6.9) for U-20 players and 70.5 (±6.1) for U-19 players. The somatotype values were 2.6-4.6-2.3 for U-20 players and 2.5-4.3-2.8 for U-19 players, with a predominance of muscle mass in all categories, characterizing them as balanced mesomorphs. CONCLUSIONS: Body composition and somatotype findings underscore distinctions in body mass across categories and playing positions, with notably higher body mass and muscle mass predominance in elevated categories. However, the prevailing skeletal muscle development establishes a significant semblance with the recognized somatotype standard for soccer. [ABSTRACT FROM AUTHOR]

Pleural mesothelioma (PM) is a highly aggressive tumor that is caused by asbestos exposure and lacks effective therapeutic regimens. Current procedures for PM diagnosis are invasive and can take a long time to reach a definitive result. Small extracellular vesicles (sEVs) have been identified as important communicators between tumor cells and their microenvironment via their cargo including circular RNAs (circRNAs). CircRNAs are thermodynamically stable, highly conserved, and have been found to be dysregulated in cancer. This study aimed to identify potential biomarkers for PM diagnosis by investigating the expression of specific circRNA gene pattern (hsa_circ_0007386) in cells and sEVs using digital polymerase chain reaction (dPCR). For this reason, 5 PM, 14 non-PM, and one normal mesothelial cell line were cultured. The sEV was isolated from the cells using the gold standard ultracentrifuge method. The RNA was extracted from both cells and sEVs, cDNA was synthesized, and dPCR was run. Results showed that hsa_circ_0007386 was significantly overexpressed in PM cell lines and sEVs compared to non-PM and normal mesothelial cell lines (p < 0.0001). The upregulation of hsa_circ_0007386 in PM highlights its potential as a diagnostic biomarker. This study underscores the importance and potential of circRNAs and sEVs as cancer diagnostic tools. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, physical activity was significantly decreased in all age groups. The purpose of this study is to investigate children's motor skills by administering an adapted physical activity program for the development of coordination skills. The sample consisted of 28 children aged 8 to 12 years, 20 neurotypical children and 8 with ASD-HF. Data collection employed various methods, including a personal information form, a leisure time exercise questionnaire, a semi-structured interview, and the Harre Dexterity Circuit for assessing physical activity improvements. The results of the two-way analysis of variance (two-way ANOVA) Tukey HSD test showed the differences between the specific groups, ASD-P vs. ASD-O (p < 0.001), ASD-O vs. AB-O (p < 0.001), ASD-O vs. AB-P (p < 0.001), ASD-O vs. AB-P (p = 0.136), ASD-P vs. AB-P (p < 0.0010, and AB-P vs. AB-O (p = 0.003). As result, both groups showed strong interest in practicing physical activity, and no statistical difference was found in doing so at home or in attendance, showing that physical activity practice is a tool for parent–child bonding and mutual enjoyment, emphasizing that the mixed approach yielded positive results in all participants. [ABSTRACT FROM AUTHOR]