TAK1 mediates an activation signal from toll-like receptor(s) to nuclear factor-κB in lipopolysaccharide-stimulated macrophages

AbstractStimulation of monocytes/macrophages with lipopolysaccharide (LPS) results in activation of nuclear factor-κB (NF-κB), which plays crucial roles in regulating expression of many genes involved in the subsequent inflammatory responses. Here, we investigated roles of transforming growth factor-β activated kinase 1 (TGF-TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), in the LPS-induced signaling cascade. A kinase-negative mutant of TAK1 inhibited the LPS-induced NF-κB activation both in a macrophage-like cell line, RAW 264.7, and in human embryonic kidney 293 cells expressing toll-like receptor 2 or 4. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated upon simulation of RAW 264.7 cells with LPS. These results indicate that TAK1 functions as a critical mediator in the LPS-induced signaling pathway

Effects of self-efficacy on oral health behaviours and gingival health in university students aged 18- or 19-years-old

Aim Although self-efficacy is known to affect various health-related practises, few studies have clearly examined how self-efficacy correlates with oral health behaviors or the oral health condition. We examined the relationship between gingivitis, oral health behaviors and self-efficacy in university students. Material & Methods A total of 2,111 students (1,197 males, 914 females) aged 18 and 19 years were examined. The degree of gingivitis was expressed as the percentage of bleeding on probing (%BOP). Additional information was collected via a questionnaire regarding oral health behaviors (daily frequency of tooth-brushing, use of dental floss and regular check-up). Self-efficacy was assessed using the Self-Efficacy Scale for Self-care (SESS). Path analysis was used to test pathways from self-efficacy to oral health behaviors and %BOP. Results In the final structural model, self-efficacies were related to each other, and they affected oral health behaviors. Good oral health behaviors reduced dental plaque and calculus, and lower levels of dental plaque and calculus resulted in lower %BOP. Conclusion Higher self-efficacy correlated with better oral health behaviours and gingival health in university students. Improving self-efficacy may be beneficial for maintaining good gingival health in university students. To prevent gingivitis, the approach of enhancing self-efficacy in university students would be useful

Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage

神経幹細胞の運命を決める分子を発見 --脳形成機構の解明と脳腫瘍や精神疾患の治療法に期待--. 京都大学プレスリリース. 2020-09-28.During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias. While the regulation of neurogenesis is well characterized, specific markers for glial precursor cells (GPCs) and the master regulators for gliogenesis remain unidentified. Accumulating evidence suggests that RNA-binding proteins (RBPs) have significant roles in neuronal development and function, as they comprehensively regulate the expression of target genes in a cell-type-specific manner. We systematically investigated the expression profiles of 1, 436 murine RBPs in the developing mouse brain and identified quaking (Qk) as a marker of the putative GPC population. Functional analysis of the NSC-specific Qk-null mutant mouse revealed the key role of Qk in astrocyte and oligodendrocyte generation and differentiation from NSCs. Mechanistically, Qk upregulates gliogenic genes via quaking response elements in their 3′ untranslated regions. These results provide crucial directions for identifying GPCs and deciphering the regulatory mechanisms of gliogenesis from NSCs

Preventive effects of trehalose on osteoclast differentiation in rat periodontitis model

Aim Trehalose, which is a disaccharide formed by a 1,1 linkage of two glucose molecules, was suggested to have a suppressive effect on bone resorption. In this study, we examined the effects of topical application of trehalose on osteoclast differentiation in a rat periodontitis model. Material and Methods Rats were divided into four groups. One group received no treatment. In the other groups, experimental periodontitis was induced by ligature placement. These rats with experimental periodontitis received topical application of pure water (vehicle group), 30 mg/ml trehalose solution (30 mg/ml trehalose group) or 60 mg/ml trehalose solution (60 mg/ml trehalose group) to the gingival sulcus respectively. Results The vehicle group showed higher numbers of polymorphonuclear leucocytes, receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells and osteoclasts compared with the no treatment group respectively. Trehalose-applied groups exhibited lower numbers of these cells compared with the vehicle group. Gene expressions of tumour necrosis factor-a, RANKL and toll-like receptor 4 were suppressed by trehalose. In addition, protein expressions of RANKL inducing pathway were less activated by trehalose. Conclusion Topical application of trehalose could suppress osteoclast differentiation by inactivation of RANKL inducing pathway in the rat periodontitis model

Awareness of Clenching and Underweight are Risk Factors for Onset of Crowding in Young Adults: A Prospective 3-Year Cohort Study

Bruxism is a parafunctional activity that can seriously affect quality of life. Although bruxism induces many problems in the oral and maxillofacial area, whether it contributes to the onset of malocclusion remains unclear. The purpose of this prospective cohort study was to investigate the association between the onset of malocclusion and awareness of clenching during the daytime in young adults. Among 1,092 Okayama University students who underwent normal occlusion at baseline, we analysed 238 who had undergone a dental examination and had complete data after 3 years (2013⁻2016). We also performed subgroup analysis to focus on the association between awake bruxism and the onset of crowding (n = 216). Odds ratios (ORs) were calculated using multivariate logistic regression analyses. The incidences of malocclusion and crowding were 53.8% and 44.5%, respectively. In multivariate logistic regression, awareness of clenching was a risk factor for crowding (OR: 3.63; 95% confidence interval [CI]: 1.08⁻12.17). Moreover, underweight (body mass index < 18.5 kg/m²) was related to the onset of malocclusion (OR: 2.34; 95%CI: 1.11⁻4.92) and crowding (OR: 2.52, 95%CI: 1.25⁻5.76). These results suggest that awareness of clenching during the daytime and underweight are risk factors for the onset of crowding in young adults

Effects of exercise training on gingival oxidative stress in obese rats

Objective: The purpose of the present study was to investigate the effects of exercise training on serum reactive oxygen species (ROS) level and gingival oxidative stress in obese rats fed a high-fat diet. Design: Rats were divided into three groups (n = 14/group): one control group (fed a regular diet) and two experimental groups (fed a high-fat diet with and without exercise training [treadmill: 5 days/week]). The rats were sacrificed at 4 or 8 weeks. The level of serum reactive oxidative metabolites (ROM) was measured as an indicator of circulating ROS. The level of 8-hydroxydeoxyguanosine (8-OHdG) and reduced-form glutathione (GSH)/oxidised-form glutathione (GSSG) ratio were determined to evaluate gingival oxidative stress. Results: The obese rats fed a high-fat diet without exercise training showed higher serum ROM levels [Carratelli Units (CARR U)] (mean +/- SD; 413 +/- 64) than the control (333 +/- 12) at 4 weeks (p = 0.023). Such a condition resulted in higher 8-OHdG levels (ng/mg mtDNA) (0.97 +/- 0.18) (p < 0.05) and a lower GSH/GSSG ratio (17.0 +/- 3.1) (p < 0.05) in gingival tissues, compared to the control (0.55 +/- 0.13 for 8-OHdG and 23.6 +/- 5.8 for GSH/GSSG ratio) at 8 weeks. In addition, the obese rats fed a high-fat diet with exercise training showed lower serum ROM (623 +/- 103) (p<0.001) and gingival 8-OHdG levels (0.69 +/- 0.17) (p = 0.012) than those without exercise training (1105 95 for ROM and 0.55 +/- 0.13 for 8-OHdG) at 8 weeks. Conclusions: Obesity prevention by exercise training may effectively suppress gingival oxidative stress by decreasing serum ROS in rats

Occlusal disharmony induces BDNF level in rat submandibular gland

Objectives: Brain-derived neurotrophic factor (BDNF), which is produced in rat submandibular gland, is one of the most abundant neurotrophins in the central nervous system. It is generally accepted that occlusal disharmony causes stress. The purpose of the present study was to investigate whether occlusal disharmony-induced chronic stress affects BDNF levels and morphology in rat submandibular gland. Design: Eight wks old male Wistar rats (n = 21) were randomly divided into three groups of 7 rats. In a control (C) group, the rats received no treatment for 8 wks. In a molar cusp-less (OD) group, maxillary molar cusps were cut off with a dental turbine at baseline and kept for 8 wks. In a molar cusp-less + recovered cusp (OR) group, maxillary molar cusps were cut off and then were recovered after 4 wks using resin material. After the experimental period, expression of BDNF mRNA and protein as well as histological findings were evaluated in the submandibular glands. The comparisons between the groups were made using the Mann-Whitney U test with Bonferroni correction. Results: The OD group showed a significant increase in submandibular gland BDNF mRNA and protein expression after 8 wks, and plasma adrenocorticotropic hormone and corticosterone levels increased in a time-dependent manner. There were no significant differences in BDNF expression in the submandibular glands and in levels of plasma adrenocorticotropic hormone and corticosterone between the OR and C groups. Conclusions: These results indicate that psychological stress induced by occlusal disharmony reversibly induces BDNF expression in the rat submandibular gland

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T_H17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T_H17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota