Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

Differentially expressed miRNAs associated with generalized aggressive periodontitis.

OBJECTIVE: This study aimed to investigate miRNA expression profiles in individuals with periodontitis which is a chronic inflammatory condition affecting the integrity of the periodontal attachment. miRNAs play a crucial role in gene regulation through various mechanisms, making them potential diagnostic markers and therapeutic targets for various diseases. MATERIALS AND METHODS: A total of 25 individuals with aggressive periodontitis and 25 controls were included in the study. Gingival tissues were collected for miRNA isolation and cDNA synthesis. miRNAs associated with periodontitis, including hsa-miR-185-5p, hsa-miR-17, hs-miR-146a, hs-miR-146b, hs-miR-155, hs-miR-203, hs-miR-205, hs-miR-223, and hsa-miR-21-3p, were analyzed using a combination of miRTarBase database analysis and literature mining was performed. Real-time PCR was used to assess the expression patterns of the target miRNAs, and the data were analyzed using the REST program. RESULTS: The study revealed upregulated expression levels of hsa-miR-223-3p, hsa-miR-203b-5p, hsa-miR-146a-5p, hsa-miR-146b-5p, and hsa-miR-155-5p in individuals with periodontitis. Conversely, downregulated expression was observed for hsa-miR-185-5p, hsa-miR-21-3p, and hsa-miR-17-3p. CONCLUSION: The findings suggest significant differences in the expression of specific miRNAs associated with inflammation in periodontitis. MZB1 acts as a hormone-regulated adipokine/pro-inflammatory cytokine, driving chronic inflammation and influencing cellular expansion. Predominantly expressed in marginal zone and B1 B cells, specialized subsets that respond rapidly to infections, MZB1 impacts immune protein synthesis and immune cell maturation, notably targeting microRNA-185 to potentially impede T cell development. Further research is needed to elucidate the functional significance and potential implications of these miRNAs. CLINICAL RELEVANCE: miRNAs regulate the expression of target genes by finely tuning protein expression levels. The current findings provide compelling evidence of notable variations in the expression levels of specific miRNAs associated with inflammation in individuals affected by periodontitis; hence, miRNAs hold promise as potential therapeutic targets for periodontitis.

Immobilization of a Bifidobacterial Endo-ß-N-Acetylglucosaminidase to Generate Bioactive Compounds for Food Industry.

Conjugated N-glycans are considered next-generation bioactive prebiotic compounds due to their selective stimulation of beneficial microbes. These compounds are glycosidically attached to proteins through N-acetylglucosamines via specific asparagine residue (AsN-X-Ser/Thr). Certain bacteria such as Bifidobacterium longum subspecies infantis (B. infantis) have been shown to be capable of utilizing conjugated N-glycans, owing to their specialized genomic abilities. B. infantis possess a unique enzyme, Endo-ß-N-acetylglucosaminidase (EndoBI-1), which cleaves all types of conjugated N-glycans from glycoproteins. In this study, recombinantly cloned EndoBI-1 enzyme activity was investigated using various immobilization methods: 1) adsorption, 2) entrapment-based alginate immobilization, 3) SulfoLink-, and 4) AminoLink-based covalent bonding immobilization techniques were compared to develop the optimum application of EndoBI-1 to food processes. The yield of enzyme immobilization and the activity of each immobilized enzyme by different approaches were investigated. The N-glycans released from lactoperoxidase (LPO) using different immobilized enzyme forms were characterized using MALDI-TOF mass spectrometry (MS). As expected, regardless of the techniques, the enzyme activity decreased after the immobilization methods. The enzyme activity of adsorption and entrapment-based alginate immobilization was found to be 71.55% ± 0.6 and 20.32% ± 3.18, respectively, whereas the activity of AminoLink- and SulfoLink-based covalent bonding immobilization was found to be 58.05 ± 1.98 and 47.49% ± 0.30 compared to the free form of the enzyme, respectively. However, extended incubation time recovery achieved activity similar to that of the free form. More importantly, each immobilization method resulted in the same glycan profile containing 11 different N-glycan structures from a model glycoprotein LPO based on MALDI-TOF MS analysis. The glycan data analysis suggests that immobilization of EndoBI-1 is not affecting the enzyme specificity, which enables full glycan release without a limitation. Hence, different immobilization methods investigated in this study can be chosen for effective enzyme immobilization to obtain bioactive glycans. These findings highlight that further optimization of these methods can be a promising approach for future processing scale-up and commercialization of EndoBI-1 and similar enzymes.