Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice.

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5-10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG.

The relationships between ACTN3 rs1815739 and PPARA-α rs4253778 gene polymorphisms and athletic performance characteristics in professional soccer players.

BACKGROUND: Current research on athletic performance focuses on genetic variants that contribute significantly to individuals' performance. ACTN3 rs1815739 and PPARA-α rs4253778 gene polymorphisms are variants frequently associated with athletic performance among different populations. However, there is limited research examining the pre-and post-test results of some variants of athletic performance in soccer players. Therefore, the presented research is to examine the relationships between the ACTN3 rs1815739 and PPARA-α rs4253778 gene polymorphisms and athletic performance improvement rates in adaptations to six weeks of training in elite soccer players using some athletic performance tests. METHODOLOGY: Twenty-two soccer players between the ages of 18 and 35 voluntarily participated in the study. All participants were actively engaged in a rigorous six-day-a-week training program during the pre-season preparation period. Preceding and following the training program, a battery of diverse athletic performance tests was administered to the participants. Moreover, Genomic DNA was extracted from oral epithelial cells using the Invitrogen DNA isolation kit (Invitrogen, USA), following the manufacturer's protocol. Genotyping was conducted using real-time PCR. To assess the pre- and post-test performance differences of soccer players, the Wilcoxon Signed Rank test was employed. RESULTS: Upon analyzing the results of the soccer players based on the ACTN3 genotype variable, it was observed that there were no statistically significant differences in the SJ (Squat Jump), 30m sprint, CMJ (Counter Movement Jump), and DJ (Drop Jump) performance tests (p > 0.05). However, a statistically significant difference was identified in the YOYO IRT 2 (Yo-Yo Intermittent Recovery Test Level 2) and 1RM (One Repetition Maximum) test outcomes (YOYO IRT 2: CC, CT, and TT, p = 0.028, 0.028, 0.008, 0.000, respectively; 1RM: CC, CT, and TT, p = 0.010, 0.34, 0.001, respectively). Regarding the PPARA-α genotype variable, the statistical analysis revealed no significant differences in the SJ, 30m sprint, CMJ, and DJ performance tests (p > 0.05). Nevertheless, a statistically significant difference was observed in the YOYO IRT 2 and 1RM test results (YOYO IRT 2: CC, CG p = 0.001, 0.020; 1RM: CC, p = 0.000) CONCLUSIONS: The current study demonstrated significant enhancements in only YOYO INT 2 and 1RM test outcomes across nearly all gene variants following the six-day-a-week training program. Other performance tests, such as the 30m sprint, SJ, CMJ, and DJ tests did not exhibit statistically significant differences. These findings contribute novel insights into the molecular processes involving PPARA-α rs4253778 and ACTN3 rs1815739 that underpin enhancements in endurance (YOYO INT 2) and maximal strength (1RM) aspects of athletic performance. However, to comprehensively elucidate the mechanisms responsible for the association between these polymorphisms and athletic performance, further investigations are warranted. It is thought that the use of field and genetic analyses together to support each other will be an important detail for athletes to reach high performance.

Vitamin B12 deficiency among asymptomatic healthy infants: its impact on the immune system.

BACKGROUND: The immunomodulatory effects of vitamin B12 deficiency in children have not yet been established in the literature. In the current study, the effects of vitamin B12 on the immune system in asymptomatic and otherwise healthy infants have been studied. METHODS: The study was conducted at Marmara University, "well-child" outpatient clinic. Vitamin B12 level was measured in a cohort of 611 healthy term infants, followed regularly for at least 6 months. Immunoglobulin measurements, lymphocyte subset analysis, cytokine production analysis, lymphocyte proliferation assays and evaluation of lymphocyte apoptosis were performed in a subset of 60 infants. RESULTS: In this cohort, one out of three babies displayed vitamin B12 deficiency. The percentage of CD4+CD25+ regulatory T cells (Tregs) was lower in vitamin B12 deficient babies than in controls. Although the percentage of Tregs increased after treatment, the change was not significant. There was no difference of cytokine levels between vitamin B12 deficient and control groups. However, proinflammatory cytokines were reduced after treatment. No significant difference was observed for immunoglobulins, early apoptosis and lymphocyte proliferation. CONCLUSIONS: Vitamin B12 deficiency is an underestimated health problem among the developing countries. The clinical consequences of the decreased percentage of Tregs associated with vitamin B12 deficiency, and reduction of proinflammatory cytokines after vitamin supplementation needs to be further studied, especially in terms of emerging allergies, autoimmune disorders and anti-inflammatory effects.

Effect of topically applied hyaluronic acid on pain and palatal epithelial wound healing: An examiner-masked, randomized, controlled clinical trial.

BACKGROUND: This study aims to evaluate the effects of two different concentrations of topical hyaluronic acid (HA) on postoperative patient discomfort and wound healing of palatal donor sites after free gingival graft (FGG) surgery. METHODS: Thirty-six patients requiring FGG were randomly assigned into three groups in an examiner-masked, randomized, controlled clinical trial. After harvesting palatal grafts, 0.2% and 0.8% HA gels were used in test groups 1 and 2, respectively. Gels were applied on donor sites and protected with periodontal dressing in the test groups, whereas the wound was covered only with periodontal dressing in the control group. On days 3, 7, 14, and 21, pain and burning sensation were recorded using a visual analog scale (VAS) as well as other parameters such as complete epithelization (CE) and color match on days 3, 7, 14, 21, and 42. RESULTS: Test groups experienced less pain than the control group on days 3 and 7 (P <0.001 and P <0.001, respectively). Mean VAS score for burning sensation was higher in the control group on day 3 compared with test groups 1 and 2 (P = 0.03 and P = 0.02, respectively). CE in all patients was achieved on day 21 in both test groups, whereas it was achieved on day 42 in the control group. The test groups showed higher color match scores than the control group on days 21 (P <0.001 and P <0.001, respectively) and 42 (P = 0.004 and P = 0.002, respectively). CONCLUSION: Topical application of HA exhibits positive impact on postoperative pain and burning sensation, and accelerates palatal wound healing in terms of epithelization and color match.

Evaluation of the Effectiveness of Esterified Hyaluronic Acid Fibers on Bone Regeneration in Rat Calvarial Defects.

Hyaluronic acid (HA) constitutes one of the major components of the extracellular matrix domain in almost all mammals. The aim of this study was to evaluate the regenerative capacity of HA matrix in rat calvarial bone defects and compare with those of different combinations of resorbable collagen membrane (M) and bovine-derived xenograft (G). Twenty-four 3-month-old male Sprague-Dawley rats weighing 200-250 g were included. Control group was created by leaving one defect empty from 2 critical size defects with 5 mm diameter formed in the calvarial bones of 8 rats. In the same rats, the other defect was treated with HA matrix alone. One of the 2 defects formed in other 8 rats was treated with HA+G and the other with HA+M. One of the 2 defects formed in the remaining 8 rats was treated with G+M and the other with HA+G+M. The animals were sacrificed at 4 weeks. Histologic, histomorphometric, and immunohistochemical analyses were performed. Both HA matrix alone and its combinations with G and M supported new bone formation (NBF). However, NBF was significantly greater in G+M and HA+G+M groups compared to control and HA alone (P<0.001). Bone morphogenetic protein-2 was expressed with varying degrees in all groups, without any difference among them. Within the limitations of the present study, HA matrix, used alone or in combination with G and M, did not contribute significantly to bone regeneration in rat calvarial bone defects.

The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles.

Aim. To compare the effects of various mesenchymal stem cells, those isolated from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells (DPSCs), and dental follicle stem cells (DFSCs), on human peripheral blood mononuclear cells (PBMCs). Method. Mesenchymal stem cells were isolated from three sources in the orofacial region. Characterization and PCR analyses were performed. Lymphocytes were isolated from healthy peripheral venous blood. Lymphocytes were cocultured with stem cells in the presence and absence of IFN-γ and stimulated with anti-CD2, anti-CD3, and anti-CD28 for 3 days. Then, lymphocyte proliferation, the number of CD4(+)FoxP3(+) T regulatory cells, and the levels of Fas/Fas ligand, IL-4, IL-10, and IFN-γ in the culture supernatant were measured. Results. The DFSCs exhibited an enhanced differentiation capacity and an increased number of CD4(+)FoxP3(+) T lymphocytes and suppressed the proliferation and apoptosis of PBMCs compared with SHEDs and DPSCs. The addition of IFN-γ augmented the proliferation of DFSCs. Furthermore, the DFSCs suppressed IL-4 and IFN-γ cytokine levels and enhanced IL-10 levels compared with the other cell sources. Conclusion. These results suggest that IFN-γ stimulates DFSCs by inducing an immunomodulatory effect on the PBMCs of healthy donors while suppressing apoptosis and proliferation and increasing the number of CD4(+)FoxP3(+) cells.

Gingival unit transfer using in the Miller III recession defect treatment.

The most significant factor for the success in soft tissue grafts is the synergistic relation between vascular configuration and involved tissues. In the soft tissue graft procedures, site specific donor tissue is assumed to have improved potential for function and aesthetic survive at recipient sites. On a clinical level, using site specific gingival unit graft that placed on traditionally prepared recipient site, results in predictable root coverage. In this case report the clinical effectiveness of gingival unit transfer (GUT) technique performed on Miller III recession was presented and a similar recession case treated with free gingival graft (FGG) technique for comparison. Probing depth, recession depth, keratinized tissue width and clinical attachment level clinical parameters were measured at baseline and postoperative 8 mo. Percentage of defect coverage was evaluated at postoperative 8 mo. Creeping attachment was assessed at postoperative 1, 3, 6 and 8 mo. The GUT revealed better defect coverage and creeping attachment results than the FGG in the treatment of Miller III defects.

Treatment of localized gingival recessions using gingival unit grafts: a randomized controlled clinical trial.

BACKGROUND: One of the success factors in periodontal plastic surgery is the synergistic relationship between involved tissues and vascular supply. Gingiva as a functional unit is unique with a specific vascular configuration and contains the supracrestal portion naturally created to survive over avascular root surfaces. The aim of this randomized controlled trial is to clinically evaluate the treatment of localized gingival recessions by using gingival unit grafts (palatal tissue involving marginal gingiva and papillae) compared with conventional palatal grafts. METHODS: Seventeen patients with Class I to II recession defects on mandibular anterior teeth were included and randomly divided into two groups. Recessions were treated with gingival unit grafts in group 1 (n = 8) and with palatal grafts in group 2 (n = 9). Clinical parameters including vertical recession (VR), probing depth, keratinized tissue (KT), and attachment level were recorded at baseline and 8 months after surgery. RESULTS: Both treatments produced significant clinical improvements within the groups. Intergroup comparison revealed significantly higher VR reduction, attachment, and KT gain in group 1 than in group 2; mean percentages of the defect coverage were 91.62% ± 9.74% and 68.97% ± 13.67%, respectively (P <0.05). Healing of the gingival unit donor site was uneventful. CONCLUSION: Within its limits, this study demonstrates the possibility of treating buccal recessions with gingival unit grafts as an alternative technique using gingival donor graft of site-specific vascular configuration, with better defect coverage, clinical, and esthetic improvements compared with palatal grafts.