Maria Balta

• Balta, Maria; Schreurs, Olaf Joseph Franciscus; Blix, Inger Johanne Schytte & Schenck, Karl (2024). The effect of resolvin D1<inf>n-3 DPA</inf> on primary oral epithelial cell migration in vitro. European Journal of Oral Sciences. ISSN 0909-8836. doi: 10.1111/eos.12981. Full text in Research Archive Show summary

  Specialized pro-resolving lipid mediators (SPMs) are known for their anti-inflammatory and pro-resolving actions. The aim of the present study was to find new functions of the SPM resolvin D1n-3 DPA (RvD1n-3 DPA) on oral epithelial cells. As a starting point, we used a dataset obtained by RNA high-throughput sequencing of oral epithelial cells exposed to TNF-α and RvD1n-3 DPA versus TNF-α alone. GOrilla enrichment analysis showed that the actin cytoskeleton was significantly overrepresented after adjustment for multiple hypothesis testing. As actin, amongst others, is closely related to cell migration, we then explored whether RvD1n-3 DPA can modulate oral epithelial cell migration. To this end, we used an in vitro cell migration model, including TNF-α treatment, to mimic an inflammatory cell state. The analysis revealed that RvD1n-3 DPA increased oral epithelial cell migration in the presence but not in the absence of TNF-α. Addition of RvD1n-3 DPA also induced F actin accumulation around the cell nucleus, indicating that RvD1n-3 DPA potentially can mediate processes of intracellular transport. This indicates that this lipid mediator may be a promising therapeutic candidate in oral mucosal wound healing.

• Aikaterini, Liatsi; Andreas, Agouropoulos; Balta, Maria; Athanasia, Tsiligianni & Sotiria, Gizani (2023). Long-term outcome of oral health in uncooperative children with caries treated under general anesthesia. Journal of Clinical Pediatric Dentistry. ISSN 1053-4628. 47(3), p. 64–70. doi: 10.22514/jocpd.2023.024. Full text in Research Archive Show summary

  Although uncooperative children with extensive caries can be treated under general anesthesia (GA), they remain at high-risk for caries recurrence. This study aimed to assess the long-term outcome of the dental health of uncooperative healthy children (HC) and special needs patients (SNP) treated under GA at least 2 years before this study. Data were collected via questionnaire and oral examination. Oral hygiene was assessed using the Hygiene Index, while caries were recorded using ICDAS II. The dmfs/DMFS score was calculated for every participant. A total of 69 patients completed the questionnaire, and 37 were clinically examined (HC = 15, SNP = 22). The mean (±SD-standard diviation) follow-up time was 5.5 (±2.55) years, the mean DMFS score for HC was 6.39 (±4.99), and the mean DMFS score for SNP was 12.95 (±12.29). The SNP group had significantly more filled surfaces on permanent teeth than the HC group (6.18 (±6.17) vs. 1.54 (±3.27), p = 0.004). In regard to primary teeth, HC had a higher dmfs, indicating a clear trend for more decayed surfaces in this group of participants (p = 0.08). The DMFS score was significantly higher in children who underwent GA more than 5 years ago. Oral health-related behavior was not improved as expected. Altogether, HC and SNP have poor oral hygiene and high caries risk in primary and permanent dentition, and their treatment remains challenging.

• Balta, Maria (2023). Vital Pulp Therapy of Young First Permanent Molars: A Retrospective Study on Radiographic Findings 24 Months Post-treatment. Oral Health & Preventive Dentistry. ISSN 1602-1622. Full text in Research Archive
• Balta, Maria G.; Schreurs, Olaf Joseph Franciscus; Halder, Rashi; Küntziger, Thomas M.; Sætre, Frank Ove & Blix, Inger Johanne Schytte [Show all 9 contributors for this article] (2022). RvD1n-3 DPA Downregulates the Transcription of Pro-Inflammatory Genes in Oral Epithelial Cells and Reverses Nuclear Translocation of Transcription Factor p65 after TNF-α Stimulation. International Journal of Molecular Sciences. ISSN 1661-6596. 23(23), p. 1–11. doi: 10.3390/ijms232314878. Full text in Research Archive Show summary

  Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1n-3 DPA and that cultured OECs respond to RvD1n-3 DPA addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1n-3 DPA–signaling in OECs under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-a-stimulated cells that were subsequently treated with RvD1n-3 DPA and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-kB) target genes. Further bioinformatics analyses showed that RvD1n-3 DPA inhibited the expression of several genes involved in the NF-kB activation pathway. Confocal microscopy revealed that addition of RvD1n-3 DPA to OECs reversed TNF-a-induced nuclear translocation of NF-kB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1n-3 DPA increases nuclear export of p65. Taken together, our observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established.

• Balta, Maria; Papathanasiou, Evangelos; Blix, Inger Johanne S. & Dyke, T E Van (2021). Host Modulation and Treatment of Periodontal Disease. Journal of Dental Research. ISSN 0022-0345. 100, p. 798–809. doi: 10.1177/0022034521995157. Full text in Research Archive
• Balta, Maria (2021). Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19. Frontiers in Immunology. Full text in Research Archive
• Balta, Maria & Kalogirou, Eleni-Marina (2021). Tumors of the labial mucosa: a retrospective study of 1045 biopsies. Medicina Oral. ISSN 1698-4447. Full text in Research Archive
• Schreurs, Olaf Joseph Franciscus; Balta, Maria; Karatsaidis, Andreas & Schenck, Karl (2020). Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus. European Journal of Oral Sciences. ISSN 0909-8836. 128(5), p. 369–378. doi: 10.1111/eos.12732. Full text in Research Archive Show summary

  Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin‐α3γ2, integrin‐α6β4, CD151, collagen α‐1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642‐phosphorylation at the basement membrane, and deposits of laminin‐α3 and laminin‐γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.

• Schreurs, Olaf Joseph Franciscus; Karatsaidis, Andreas; Balta, Maria; Grung, Bjarte; Hals, Else Kristine Breivik & Schenck, Karl (2020). Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus. European Journal of Oral Sciences. ISSN 0909-8836. 128(1), p. 7–17. doi: 10.1111/eos.12666. Full text in Research Archive Show summary

  Keratins form intermediate filaments of the cytoskeleton in keratinocytes and have roles in cell structure, signaling, intracellular transport, and cell death. Oral lichen planus (OLP) is an oral inflammatory disease with derangements in basal keratinocytes and disruption of the basal membrane. Here, we focused on epithelial expression of keratins 8, 18, and 19 because these proteins are known to modulate cell death. Biopsies were taken from buccal oral mucosa of persons with normal oral mucosa (n = 10) or atrophic OLP (n = 10). Cultured normal oral keratinocytes (n = 4) showed expression of mRNA and protein for keratins 8, 18, and 19. Immunohistochemistry showed consistent staining for keratins 8 and 18 in basal keratinocytes of normal oral mucosa. In OLP, staining for keratin (K)8 was mostly negative and staining for K18 was weak. Keratin 19 was expressed irregularly in most biopsies of normal oral mucosa and not at all in OLP. Several mononuclear leukocytes in the cellular infiltrate showed membrane staining for K8 and K18. Positive staining for K16 confirmed partial collapse of the basal cell layer in OLP. The basal cell niche in OLP therefore appeared to be partly populated with keratinocytes demonstrating a higher degree of differentiation (K8− K18− K19− K16+); consequently, such areas may be more susceptible to the action of cell death factors released from the cell infiltrate as a result of lacking the protective, normal keratin present in the basal epithelial cell layer of normal oral mucosa.

• Balta, Maria (2020). Periodontal therapy increases neutrophil extracellular trap degradation. Innate Immunity. ISSN 1753-4259. Full text in Research Archive
• Moonen, Carolyn GJ; Buurma, Kirsten GD; Faruque, Mouri RJ; Balta, Maria; Liefferink, Erol & Bizzarro, Sergio [Show all 8 contributors for this article] (2019). Periodontal therapy increases neutrophil extracellular trap degradation. Innate Immunity. ISSN 1753-4259. doi: 10.1177/1753425919889392. Full text in Research Archive Show summary

  In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the ex vivo NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.

• Balta, Maria (2019). European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study. Journal of Clinical Periodontology. ISSN 0303-6979. Full text in Research Archive
• Balta, Maria (2017). Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1. Frontiers in Immunology. doi: 10.3389/fimmu.2017.01682. Full text in Research Archive

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