Age and sex disparities in Latin-American adults with gliomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify if there are ethnic differences in the age and sex distribution of gliomas in the Latino adult population. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Databases used were MEDLINE, LILACS, Web of Science, and Scopus. Studies were included if they reported the age and/or sex distribution of gliomas in Latin adults, published in English or Spanish from January 1st, 1985, to December 1st, 2022. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale and the NIH Quality Assessment Tool. RESULTS: From 1096 articles, fifteen studies with information on 6,815 patients were selected for the systematic review, and thirteen were selected for the meta-analysis. The mean ages of diagnosis of glioma and glioblastoma were 50.9, 95\%\ CI [47.8-53.9] years and 53.33 years, 95 \% CI [51-55.6], respectively. The male-to-female incidence rate ratio of gliomas was 1.39. CONCLUSION: Our study found mean ages of glioma and glioblastoma were 6 and 10 years lower than those reported in the CBTRUS. Our study suggests disparities in the age and sex distribution of gliomas in Latin America compared to other regions. PROSPERO REGISTRATION NUMBER: CRD42021274423.

Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages.

Vasoactive intestinal peptide (VIP) was originally isolated as a vasodilator intestinal peptide, then as a neuropeptide. In the immune system, VIP is described as an endogenous macrophage-deactivating factor. VIP exerts its immunological actions in a paracrine and/or autocrine manner, through specific receptors. However, very little is known about the molecular regulation of VIP type 2 receptor (VPAC(2)) in the immune system. We now report that different toll-like receptor (TLR) ligands selectively regulate the VPAC(2) receptor gene and show a gene repression system controlled by key protein kinase signalling cascades in macrophages. VPAC(2) gene expression is regulated by gram-positive (TLR2 ligands) and gram-negative bacteria wall constituents (TLR4 ligands). Moreover, VPAC(2) is tightly regulated: TLR2- or TLR2/6- but not TLR2/1-mediated mechanisms are responsible for the induction of VPAC(2). TLR stimulation by viral or bacterial nucleic acids did not modify the VPAC(2) mRNA levels. Remarkably, imiquimod--a synthetic TLR7 ligand--led to a potent up-regulation of VPAC(2) gene expression. TLR5 stimulation by flagellin present in gram-positive and gram-negative bacteria did not affect VPAC(2) mRNA. The p38 mitogen-activated protein kinase (MAPK) activity accounted for the TLR4-mediated induction of VPAC(2) gene expression. Surprisingly, our data strongly suggest for the first time a tightly repressed control of VPAC(2) mRNA induction by elements downstream of MAPK kinase 1/2, PI3K/Akt, and particularly Jun-NH(2)-terminal kinase signalling pathways.

The modulatory role of melatonin on immune responsiveness.

Afterhe successful discovery of the melatonin molecule by Aaron B Lerner et al at Yale University in 1958, melatonin and the pineal gland, a tiny endocrine gland situated at the center of the human brain, have primarily been considered in terms of their effects on the endocrine and reproductive systems. During the last decade, a substantial body of research has defined melatonin as a remarkable molecule with pleiotropic effects on the immune system. Moreover, its synthesis cannot be considered as exclusively endocrine; key immunocompetent cells have the functional enzymatic machinery for melatonin synthesis, paving the wayfo r complex intracrine, autocrine and paracrine regulatory loops. The immunomodulatory role of melatonin, with regard to infection, inflammation and autoimmunity, is outlined here, and the evidence discussed in this review strengthens the notion that the nature of an immune response may be modified, and therefore therapeutically manipulated, by circadian effector signals.

Protective role for plasmid DNA-mediated VIP gene transfer in non-obese diabetic mice.

Studies focused on the development of diabetes in NOD mice-a model for human type 1 diabetes-have revealed that an autoimmune inflammatory process is produced by the effect of Th1 cells and their secreted cytokines. DNA vaccination has been shown to be an effective method for modulating immunity in viral infections and experimental autoimmune diseases, including diabetes. VIP's immunomodulatory properties are partly mediated by skewing the pattern of cytokines from a proinflammatory response to an anti-inflammatory response. Using gene delivery to express VIP, we interfered in the immune process leading to diabetes in prone, cyclophosphamide-treated NOD mice. Our results extend the role of VIP in the control of immunoregulatory networks and open new perspectives for immunointervention through VIP-based gene therapy.

NAP, a peptide derived from the activity-dependent neuroprotective protein, modulates macrophage function.

NAP is an eight-amino acid neuroprotective peptide NAPVSIPQ; it is the smallest active element derived from the recently cloned activity-dependent neuroprotective protein (ADNP). NAP readily enters the brain from the blood. It will be important to learn whether NAP, in addition to its neuroprotective activity, also might influence immune-mediated inflammation. Here, we report that: (a) macrophages express ADNP; (b) expression of ADNP in macrophages responds to VIP; and (c) NAP downregulates the key inflammatory cytokines tumor necrosis factor (TNF-alpha), interleukin-16 (IL-16), and IL-12 in macrophages. These findings indicate that ADNP/NAP can play an important role in immune regulation as well as in neuroprotection, which may be mutually related processes.

The use of melatonin as a vaccine agent.

Molecules with immunomodulatory properties determine the magnitude and quality of immune responses specific for the coadministered antigen. Melatonin is considered a biological-response modifier of the immune system with broad application in veterinary medicine. In seasonally-breeding animals, the indolamine is able to improve reproductive performance. With the purpose of expanding new advantageous roles for melatonin, we investigated the effect of subcutaneous slow-release melatonin implants in the humoral response after a vaccination. We reported here a new feature of melatonin as an adjuvant-like system towards Dichelobacter nodosus (A1 and C serotypes)--the bacterium which cause ovine footrot--the most important cause of lameness in sheep. Antibody titres determined by both agglutination and ELISA techniques were substantially higher and were sustained for a longer duration than non-implanted animals. Remarkably, the effect of melatonin was completely dependent on the presence of aluminium hydroxide. The finding that melatonin enhances a defined immune response in vivo opens new perspectives for the improvement of Th2-biased immune responses by alum adjuvants.