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Periodontitis is a common inflammatory disease that affects the teeth-supporting tissue and causes bone and tooth loss. Moreover, in a worldwide population, periodontal disease is often associated with cardiovascular diseases. Emerging studies have reported that one of the major pathogens related to periodontitis is Porphyromonas gingivalis (P. gingivalis), which triggers the inflammatory intracellular cascade. Here, we hypothesized a possible protective effect of ascorbic acid (AA) in the restoration of the physiological molecular pathway after exposure to lipopolysaccharide derived from P. gingivalis (LPS-G). In particular, human gingiva-derived mesenchymal stem cells (hGMSCs) and endothelial-differentiated hGMSCs (e-hGMSCs) exposed to LPS-G showed upregulation of p300 and downregulation of DNA methyltransferase 1 (DNMT1), proteins associated with DNA methylation and histone acetylation. The co-treatment of AA and LPS-G showed a physiological expression of p300 and DNMT1 in hGMSCs and e-hGMSCs. Moreover, the inflammatory process triggered by LPS-G was demonstrated by evaluation of reactive oxygen species (ROS) and their intracellular localization. AA exposure re-established the physiological ROS levels. Despite the limitations of in vitro study, these findings collectively expand our knowledge regarding the molecular pathways involved in periodontal disease, and suggest the involvement of epigenetic modifications in the development of periodontitis., (© 2021. The Author(s).)

Deficit of the short stature homeobox containing gene (SHOX) accounts for 2.15% of cases of idiopathic short stature (ISS) and 50-100% of cases of Leri-Weill dyschondrosteosis (LWD). It has been demonstrated that patients with SHOX deficit show a good response to treatment with GH. Thus, the early identification of SHOX alterations is a crucial point in order to choose the best treatment for ISS and LWD patients. In this study, we analyze the most commonly used molecular techniques for the detection of SHOX gene alterations. multiple ligation-dependent probe amplification analysis appears to represent the gold standard for the detection of deletion involving the SHOX gene or the enhancer region, being able to show both alterations in a single assay.

Valproic acid (VPA), an established antiepileptic and antimanic drug, has recently emerged as a promising neuroprotective agent. Among its many cellular targets, VPA has been recently demonstrated to be an effective inhibitor of histone deacetylases. Accordingly, we have adopted a schedule of dietary administration (2% VPA added to the chow) that results in a significant inhibition of histone deacetylase activity and in an increase of histone H3 acetylation in brain tissues of 4 weeks-treated rats. We have tested this schedule of VPA treatment in an animal model of Parkinson's disease (PD), in which degeneration of nigro-striatal dopaminergic neurons is obtained through sub-chronic administration of the mitochondrial toxin, rotenone, via osmotic mini pumps implanted to rats. The decrease of the dopaminergic marker tyrosine hydroxylase in substantia nigra and striatum caused by 7 days toxin administration was prevented in VPA-fed rats. VPA treatment also significantly counteracted the death of nigral neurons and the 50% drop of striatal dopamine levels caused by rotenone administration. The PD-marker protein alpha-synuclein decreased, in its native form, in substantia nigra and striatum of rotenone-treated rats, while monoubiquitinated alpha-synuclein increased in the same regions. VPA treatment counteracted both these alpha-synuclein alterations. Furthermore, monoubiquitinated alpha-synuclein increased its localization in nuclei isolated from substantia nigra of rotenone-treated rats, an effect also prevented by VPA treatment. Nuclear localization of alpha-synuclein has been recently described in some models of PD and its neurodegenerative effect has been ascribed to histone acetylation inhibition. Thus, the ability of VPA to increase histone acetylation is a novel candidate mechanism for its neuroprotective action.

The POLG1 nuclear gene, encoding for the catalytic subunit of the mitochondrial polymerase gamma, has been reported to play a role in male infertility. In fact, genotypes showing alleles different from the common ten repeat CAG allele have been detected in patients with oligozoospermia or in patients with normal spermiograms and unexplained infertility. However, these results have been debated by other studies. To verify these data, we analyzed 625 individuals in three groups of case-controls from three different Italian regions. In these series, the frequency of the different genotypes was not statistically different in oligozoospermic vs normal subjects. Even considering the pooled controls and patients (348 and 277, respectively), no significant difference was shown (p = 0.11). Our findings, in agreement with other studies from Italy and France, suggest that, at least in these countries, the POLG1 CAG-repeat polymorphisms do not contribute to oligozoospermia.

The 677T allele of the MTHFR gene has been suggested to represent a factor of risk for male infertility. In order to confirm this association, we investigated the presence of the 677T allele in 93 Italian infertile patients, selected after the exclusion of other possible genetic causes of infertility, and in 105 Italian fertile controls. The homozygous 677TT genotype was present in 20.4% of patients and 27.6% of controls. These results do not support an association between the MTHFR 677T allele and male infertility in Italy.

Forty Italian individuals with sperm counts in the range 20-130x10(6)/ml were typed with eleven Y-specific binary markers. Five Y haplogroups (1, 2, 3, 9 and 21) were present in the sample. In Italy, in contrast to Denmark, sperm counts were similar in the different haplogroups.

We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

The long arm of the Y chromosome contains genes mapped in loci involved in male infertility, short stature and gonadoblastoma. However, many of these genes have not been fully characterized, and are not currently investigated in patients affected by such diseases. We report a study aimed to the genomic characterization of 5 genes mapped within the Y chromosome: BPY2, PRY, TTY1, TTY2, and VCY. Exon-intron boundaries were detected for each gene, and PCR analysis was carried out to investigate the involvement of these genes in different re-arrangements of the Y chromosome. It was found that BPY2 and PRY are lost in some infertile patients with Yq microdeletions, suggesting that they could play a role in male gametogenesis. On the other hand, these patients retain some copies of TTYI and TTY2 genes, due to the presence of copies in Yp, and of VCY, which has homologous copies on the X chromosome. On the basis of their localization, these genes could be candidate for the gonadoblastoma locus (TTY1, TTY2) and for the control growth locus (VCY).