A revised version of the Seirei Swallowing Questionnaire for people with cognitive decline (Swallow-10).

The Seirei dysphagia screening questionnaire (namely, Seirei dsq) has been used to screen for oropharyngeal dysphagia (OD). Some of the questions in the questionnaire are difficult for people with cognitive decline to answer. We selected 10 items from the Seirei dsq that could be assessed by others, such as care workers (named Swallow-10). This study aims to verify the validity of the scoring method used in Swallow-10. The dataset used in this study was the one used in the development of Seirei dsq : 50 patients with cerebrovascular disease who were diagnosed with OD, 145 patients with cerebrovascular disease who did not have OD, and 170 healthy subjects. Among the answer choices, "A" for severe symptom, "B" for mild symptom and "C" for no symptom were scored with 4, 1 and 0 points respectively. Factor analysis extracted two factors : one related to pharyngeal function and another related to oral function. In addition, the Cronbach's alpha coefficient was 0.84. ROC analysis indicated that optimal cutoff value was 5 points, with a sensitivity of 90.0% and a specificity of 88.5%. These results suggest that Swallow-10 may be useful as an OD screening tool for subjects with cognitive decline J. Med. Invest. 70 : 231-235, February, 2023.

Factors associated with diabetes control : results of a 2-year cohort study of outpatients with type 2 diabetes.

Type 2 diabetes is a typical lifestyle disease. We aimed to identify the factors affecting glycemic control in 64 outpatients with type 2 diabetes over a 2-year period. We defined poor glycemic control using a change in glycosylated hemoglobin (?HbA1c) of ??0.5% over 2 years and/or HbA1c ??7.5% at the end of the study period. We used a questionnaire to collect information on oral health behavior and lifestyle, including eating and smoking habits, and analyzed the relationships between indices of diabetes control and responses to the questionnaire. The mean (SD) HbA1c of the participants was 6.87% (0.77%) at a baseline, and 6.93% (0.69%) after 2 years. Twenty-three participants (36.0%) had poor glycemic control. ?HbA1c and the change in body mass index (?BMI) correlated (Spearman's rank correlation, r?=?0.350, p?

The relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult: A 6-year longitudinal study.

OBJECTIVES: The study aimed to investigate the relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult through a 6-year longitudinal study. METHODS: The participants enrolled in the cross-sectional study were 3564 Tokushima City residents aged 75, 80, 85, and 90 years old who received oral health examinations and who responded to a questionnaire on oral conditions and health behavior at baseline. The data for the occurrence of disability or mortality, and the monthly medical expenditures, dental expenditures, and total medical expenditure of each participant were obtained from the National Health Insurance Database. RESULTS: The total medical expenditure showed significant differences in participants who had difficulties in eating tough foods, difficulties in swallowing tea or soup, and dry mouth when compared to that of healthy participants, in addition to the current medical treatment against the general disease. The 6-year longitudinal study revealed that participants with subjective oral frailty symptoms, including difficulties in eating tough foods and difficulties in swallowing tea or soup at baseline, had significantly higher medical, dental, and total expenditures among 538 participants without certified nursing care. In addition, those with subjective oral frailty or with less than 19 teeth present were shown to have a higher possibility for the occurrence of disability or mortality by the cox proportional hazard analysis. Furthermore, it was found that medical and total expenditures in older adults with adverse health outcomes were higher than that of healthy participants. CONCLUSION: These results suggest that subjective oral frailty in the latter-stage older adult is related to subsequent adverse health outcomes and an increase in medical and dental expenditures.

Oral care tablet containing kiwifruit powder affects tongue coating microbiome.

OBJECTIVES: Tongue coating, a kind of biofilm formed on the tongue dorsum, is the cause of various clinical conditions, such as oral halitosis and periodontal diseases, because Fusobacterium nucleatum acts as a bridge between other oral bacteria and periodontopathogenic bacteria in biofilm formation. Our previous clinical study revealed that taking oral care tablets containing kiwifruit powder significantly reduced not only tongue-coating index and volatile sulfur compounds but also total bacteria and F. nucleatum in tongue coating. In this study, we analyzed the microbiome of tongue coating samples obtained before and after oral care tablets intake to clarify whether this tablet is a useful tool for daily tongue care. METHODS: Thirty-two healthy young adults were enrolled, and a crossover clinical trial was conducted. We instructed subjects to remove tongue coating by tongue brush for intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for intervention II. Microbial DNA was isolated from the collected tongue coating samples in each subject, then 16S rRNA next-generation sequencing, operational taxonomic unit clustering, and statistical analysis were performed. RESULTS: The microbiome analysis revealed that the oral care tablet in intervention II prompted a significant change in the tongue microbiota composition, a significant reduction in the relative abundance of Prevotella and Porphyromonas, and an increase in Firmicutes/Bacteroidetes ratio when compared to that in intervention I. CONCLUSION: These results suggested that the oral care tablet might contribute to the improvement of the oral condition due to its good influence on the tongue coating microbiome.

Effect of Jersey cow defatted dry milk on salivary volume and composition in elderly persons†:†a pilot study.

The administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK), and His59-Lys60 (HK) from ß-lactoglobulin C variant, which is specific to Jersey cow milk, has been shown to prevent and/or restore the age-dependent atrophy and functional decline of salivary glands by affecting gene expression in elderly rats. In this study, we investigated the effect of Jersey cow defatted milk on salivary volume and composition in elderly persons. Participants (aged 85 to 98, n = 8) were administered defatted dry milk from Jersey cows twice a day for 4 weeks. Before and after 4 weeks from the start of drinking, saliva was collected and weighed. Salivary cystatin S and amylase levels were analyzed by Western blotting. To assess the effect of Jersey cow defatted milk on taste perception, questionnaires were used. Salivary volume after oral administration of 40 g of Jersey cow defatted dry milk daily for 4 weeks was 1.8 times higher than that before administration. Salivary cystatin S and amylase levels significantly increased after administration of Jersey cow defatted dry milk. Moreover, all participants who had taste impairment reported improved taste perception after administration. The administration of Jersey cow defatted dry milk increased salivary volume and changed the composition of saliva in elderly persons. Furthermore, it improved taste perception. J. Med. Invest. 68 : 280-285, August, 2021.

Association between diabetes-related clinical indicators and oral health behavior among patients with type 2 diabetes.

Objective : The aim of this study was to evaluate the association between diabetes-related indicators and oral health behavior among patients with type 2 diabetes. Methods : Seventy-four outpatients were included. We administered a questionnaire and divided the patients into two groups according to oral health behavior and eating habits. We then compared diabetes-related clinical records between the groups and performed logistic regression analysis. Results : Participants who brushed their teeth before bedtime every night had lower BMIs than those who did not. Participants who reported eating slowly and chewing well every day had significantly lower HbA1c than their counterparts. Participants who reported gum bleeding had significantly higher LDL-cholesterol than their counterparts. Binominal logistic regression analysis revealed that BMI < 25 was associated with not brushing teeth before bedtime every night, HbA1c < 7.5 with not eating slowly or chewing well every day, and LDL-cholesterol < 120 with gum bleeding (odds ratio : 0.140, 95% confidence interval : 0.036-0.540 ; OR : 0.085, 95% CI : 0.010-0.736, OR : 0.275, 95% CI : 0.077-0.979, respectively). Conclusions : Our findings suggest that toothbrushing before bedtime every night is associated with reduced risk of obesity and that eating slowly and chewing well are advantageous for glycemic control in patients with type 2 diabetes.J. Med. Invest. 68 : 140-147, February, 2021.

Involvement of oral bacteria and oral immunity as risk factors for chemotherapy-induced fever with neutropenia in patients with hematological cancer.

The aim of this study is to investigate the association between chemotherapy-induced fever with neutropenia less than 1500/µL (FwN) and oral bacteria and/or oral immunity in patients with hematological cancer. Thirty-two patients with hematological cancer were enrolled in the study. Secretory immunoglobulin A (sIgA) in saliva and the anaerobic bacteria in tongue coating of each subject were assessed before the first chemotherapy. Eleven subjects had an onset of FwN and 21 subjects did not during the observation periods. It was revealed by the Cox-proportional hazard model analysis that the levels of sIgA were low (HR 0.98, p < 0.05) and the rate of Fusobacterium nucleatum [F. nucleatum count per total bacterial count (%)] was high (HR 1.65, p < 0.05) in patients with FwN onset. Using ROC curve analysis, the optimal cutoff point based on the AUC in the F. nucleatum/sIgA ratio was 0.023, and this model had a 78.4% probability (p < 0.01). The risk of FwN onset was also significantly higher among the group of ≥ 0.023 F. nucleatum/sIgA ratio (HR 66.06, p < 0.01). These results suggest that the rate of F. nucleatum and the levels of sIgA at baseline might be related to FwN onset as risk factors.

Association between Oral Health Status and Diabetic Nephropathy-Related Indices in Japanese Middle-Aged Men.

Oral health status is known to be associated with lifestyle-related diseases such as diabetes and chronic kidney disease. In Japan, around 40% of hemodialysis cases are patients with diabetic nephropathy. The aim of this study was to clarify the association between oral health status and diabetic nephropathy-related indices in Japanese middle-aged men. Sixty-six men (age range: 55-64 years) with ≥20 remaining teeth and who received public medical checkups and oral examinations were enrolled. We examined correlations of age, body mass index, HbA1c, HDL-C, LDL-C, neutral fat, serum creatinine, and the estimated glomerular filtration rate (eGFR) with the number of remaining teeth or the community periodontal index (CPI) score (periodontal pocket < 4 mm: 0, 4-6 mm: 1, ≥6 mm: 2). A positive correlation between the CPI score and serum creatinine and a negative correlation between CPI score and eGFR (Spearman's rank correlation coefficient, r = 0.459, p < 0.01, and r = -0.460, p < 0.01, respectively) were observed. The mean eGFR in the CPI score 0 group was significantly higher than that in the CPI score 1/2 group (82.6 vs. 70.7, Student's t-test, p < 0.01). Logistic regression analysis using eGFR as a dependent variable and age, CPI score, body mass index, HbA1c, and neutral fat as independent variables suggested that low eGFR (<60) could be attributed to CPI score (OR = 3.169, 95% CI: 1.031-9.742, p = 0.044). These results suggest a possible association between periodontal status and renal function in Japanese middle-aged men. Periodontal condition is controlled by oral prophylaxis, and periodontal disease and chronic kidney disease have some common risk factors. Thus, periodontal management can contribute to the prevention of severe chronic kidney disease.

Effectiveness of a digital device providing real-time visualized tooth brushing instructions: A randomized controlled trial.

INTRODUCTION: The aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions. METHODS: We conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles. RESULTS: Among 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was -20.46% in the intervention group and -15.77% in the control group (p = 0.088, 95% confidence interval -0.70-10.07). CONCLUSIONS: A digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque.

Effectiveness of an oral care tablet containing kiwifruit powder in reducing oral bacteria in tongue coating: A crossover trial.

OBJECTIVES: The aim of this study was to investigate the effect of an oral care tablet containing kiwifruit powder on oral bacteria in tongue coating compared with tongue brushing. MATERIAL AND METHODS: Thirty-two healthy, young adults were enrolled, and a crossover clinical trial was conducted. The volatile sulfur compound (VSC) concentration, Winkel tongue-coating index (WTCI), and the number of total bacteria in addition to Fusobacterium nucleatum in tongue coating were measured. We instructed subjects to remove tongue coating by tongue brush for Intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for Intervention II, and three oral care tablets 1 day before the measurement for Intervention III. RESULTS: There were significant differences in terms of the level of H2 S, VSC, and WTCI at Intervention I and all evaluation values at Intervention II. There were significant differences in terms of the level of H2 S, VSC, WTCI, the number of total bacteria, and F. nucleatum at Intervention III. The value of WTCI, the number of bacteria, and F. nucleatum decreased significantly after taking the oral care tablets than after tongue brushing. When compared with Interventions I and III, Intervention III showed the effective results; there were significant differences in the number of total bacteria and F. nucleatum between tongue brushing and taking tablets. CONCLUSIONS: These results suggested that the oral care tablet containing kiwifruit powder could be effective in reducing total bacteria and F. nucleatum in tongue coating when compared with tongue brushing.

Human airway trypsin-like protease (HAT) is released into saliva.

We first discovered human airway trypsin-like protease (HAT) in human mucoid sputum. Precursor HAT (47 kDa), a cell surface type Ⅱ transmembrane serine protease, is proteolyzed to mature HAT (27 kDa). Hitherto, HAT has not been detected in other biological fluids except for human sputum. We aimed to clarify whether human saliva contains mature HAT. Trypsin-like protease was isolated from saliva of healthy volunteers by a method adopted for isolation of HAT from sputum using Boc-Phe-Ser-Arg-MCA as the substrate. Biochemical properties of purified protease were similar to those of recombinant HAT (rHAT). HAT concentration in saliva was measured by ELISA, and immunoreactive HAT:total protein ratio (ng/mg) in saliva samples from healthy subjects was similar to that in mucoid sputum. RT-PCR showed that HAT mRNA was expressed in human gingival epithelial cells but not in gingival fibroblasts. Both indirect immunofluorescence and western blotting using monoclonal antibody for α-smooth muscle actin (α-SMA;a myofibroblast marker) showed that HAT enhanced α-SMA fiber expression in gingival fibroblasts. These results indicate that both mucoid sputum and saliva from healthy subjects have similar concentrations of mature HAT, and HAT is related to certain physiological functions and pathological states of myofibroblasts in the oral cavity. J. Med. Invest. 65:258-267, August, 2018.

Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy:a clinical trial for oral hygiene and oral condition.

OBJECTIVE: The aim of this study was to investigate the impact of the use of two Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition in patients with esophageal cancer undergoing chemotherapy. METHODS: Twenty-three esophageal cancer patients who receive chemotherapy at Tokushima University Hospital, were included. The participants, who received professional oral healthcare, were randomly divided into three groups:7 subjects received Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects received nothing (control). The numbers of total bacteria and specific periodontopathogenic bacteria in tongue coating were determined in addition to clinical parameters. RESULTS: No difference on the onset of oral mucositis was found among the three groups. However, tongue coating index, gingival index (GI), plaque index, the number of total bacteria, Fusobacterium nucleatum and Campylobacter rectus were decreased during chemotherapy. More specifically, GI as well as the number of F. nucleatum and C. rectus were decreased significantly in the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No such differences were observed for the group receiving Hangeshashinto. CONCLUSION: This clinical trial showed that Daiokanzoto might be effective in attenuating gingival inflammation and reducing the levels of periodontopathogenic bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August, 2018.

Survey on Nursing Home Caregivers' Basic Knowledge of Oral Health Management: Dental Terminology.

With the increasing numbers of the elderly requiring care in Japan, the management of their oral health care will require cooperation between medical and dental professionals, and we need to transfer dental knowledge from dental professionals to caregivers. With the help of a questionnaire, we examined 181 caregivers' depth of understanding regarding 20 typical dental terms with a view to improving the educational instruction provided to them. It was found that except for "clasp", popular dental terms have largely been accepted. The differences in their degrees of understanding could be owing to the lack of systematic education for caregivers.

A Review of Evidence for a Therapeutic Application of Traditional Japanese Kampo Medicine for Oral Diseases/Disorders.

Kampo medicines prescribed by specialized medical practitioners and Japanese physicians have gradually reemerged in Japan as alternatives to Western medications. Kampo formulations are composed of several plant extracts and, as such, the broad variety of phytochemicals they contain likely act synergistically to provide their beneficial effects. Kampo medicines have traditionally been prescribed for a number of health conditions, including chronic hepatitis, bronchial asthma, anemia, etc. The aim of this article is to review the beneficial effects of Kampos with respect to oral health. Pertinent papers published between 1970 and 2017 were retrieved by searching in PubMed, ScienceDirect, Web of Science, and Scopus using key words followed by evaluation of the relevant articles. In vitro studies have identified a number of properties that give credence to the potential of Kampos for treating or preventing oral diseases/disorders. Given their anti-microbial and anti-inflammatory properties, they may be promising agents for controlling periodontal diseases, oral mucositis, xerostomia, and drug-induced gingival overgrowth. Since some oral diseases have a complex etiology that involves microbial pathogens and the host immune response, agents with dual functionality such as Kampo phytochemicals may offer a therapeutic advantage.

Development of an Oral Assessment Sheet for Evaluating Older Adults in Nursing Homes.

A new general use oral assessment sheet (OAS), comprising three items each in three categories (i.e., oral hygiene, biting and chewing, and oral function), was developed to improve the oral health of older adults requiring nursing care. Seventy-nine care workers used the assessment sheet to evaluate oral conditions in 188 institutionalized older adults. Forty-five care workers and three dental professionals then assessed oral conditions in 45 institutionalized older adults using the test-retest method before and after dental professional guidance. Cronbach's alpha of the OAS was 0.72, and 0.65, 0.57, and 0.82 for the three subcategories of oral hygiene, biting and chewing, and oral function, respectively. After dental professional intervention, absolute and relative agreement coefficients increased to more than 0.6 and 0.89, respectively. Reliability and validity of the OAS were verified, and difficulties in oral assessment experienced by care workers were identified. [Res Gerontol Nurs. 2017; 10(5):234-239.].

Factors associated with regular dental visits among hemodialysis patients.

AIM: To investigate awareness and attitudes about preventive dental visits among dialysis patients; to clarify the barriers to visiting the dentist. METHODS: Subjects included 141 dentate outpatients receiving hemodialysis treatment at two facilities, one with a dental department and the other without a dental department. We used a structured questionnaire to interview participants about their awareness of oral health management issues for dialysis patients, perceived oral symptoms and attitudes about dental visits. Bivariate analysis using the χ(2) test was conducted to determine associations between study variables and regular dental check-ups. Binominal logistic regression analysis was used to determine factors associated with regular dental check-ups. RESULTS: There were no significant differences in patient demographics between the two participating facilities, including attitudes about dental visits. Therefore, we included all patients in the following analyses. Few patients (4.3%) had been referred to a dentist by a medical doctor or nurse. Although 80.9% of subjects had a primary dentist, only 34.0% of subjects received regular dental check-ups. The most common reasons cited for not seeking dental care were that visits are burdensome and a lack of perceived need. Patients with gum swelling or bleeding were much more likely to be in the group of those not receiving routine dental check-ups (χ(2) test, P < 0.01). Logistic regression analysis demonstrated that receiving dental check-ups was associated with awareness that oral health management is more important for dialysis patients than for others and with having a primary dentist (P < 0.05). CONCLUSION: Dialysis patients should be educated about the importance of preventive dental care. Medical providers are expected to participate in promoting dental visits among dialysis patients.

The Daiokanzoto (TJ-84) Kampo Formulation Reduces Virulence Factor Gene Expression in Porphyromonas gingivalis and Possesses Anti-Inflammatory and Anti-Protease Activities.

Kampo formulations used in Japan to treat a wide variety of diseases and to promote health are composed of mixtures of crude extracts from the roots, bark, leaves, and rhizomes of a number of herbs. The present study was aimed at identifying the beneficial biological properties of Daiokanzoto (TJ-84), a Kampo formulation composed of crude extracts of Rhubarb rhizomes and Glycyrrhiza roots, with a view to using it as a potential treatment for periodontal disease. Daiokanzoto dose-dependently inhibited the expression of major Porphyromonas gingivalis virulence factors involved in host colonization and tissue destruction. More specifically, Daiokanzoto reduced the expression of the fimA, hagA, rgpA, and rgpB genes, as determined by quantitative real-time PCR. The U937-3xκB-LUC monocyte cell line transfected with a luciferase reporter gene was used to evaluate the anti-inflammatory properties of Daiokanzoto. Daiokanzoto attenuated the P. gingivalis-mediated activation of the NF-κB signaling pathway. It also reduced the secretion of pro-inflammatory cytokines (IL-6 and CXCL8) by lipopolysaccharide-stimulated oral epithelial cells and gingival fibroblasts. Lastly, Daiokanzoto, dose-dependently inhibited the catalytic activity of matrix metalloproteinases (-1 and -9). In conclusion, the present study provided evidence that Daiokanzoto shows potential for treating and/or preventing periodontal disease. The ability of this Kampo formulation to act on both bacterial pathogens and the host inflammatory response, the two etiological components of periodontal disease, is of high therapeutic interest.

Current status of collaborative relationships between dialysis facilities and dental facilities in Japan: results of a nationwide survey.

BACKGROUND: Recent studies have reported an association between periodontal disease and mortality among dialysis patients. Therefore, preventive dental care should be considered very important for this population. In Japan, no systematic education has been undertaken regarding the importance of preventive dental care for hemodialysis patients--even though these individuals tend to have oral and dental problems. The aim of this study was to investigate the current state of collaborative relationships between hemodialysis facilities and dental services in Japan and also to identify strategies to encourage preventive dental visits among hemodialysis outpatients. METHODS: A nationwide questionnaire on the collaborative relationship between dialysis facilities and dental facilities was sent by mail to all medical facilities in Japan offering outpatient hemodialysis treatment. RESULTS: Responses were obtained from 1414 of 4014 facilities (35.2%). Among the 1414 facilities, 272 (19.2%) had a dental service department. Approximately 100,000 dialysis outpatients were receiving treatment at these participating facilities, which amounts to one-third of all dialysis patients in Japan. Of those patients, 82.9% received hemodialysis at medical facilities without dental departments. Only 87 of 454 small clinics without in-house dental departments (19.2%) had collaborative registered dental clinics. Medical facilities with registered dental clinics demonstrated a significantly more proactive attitude to routine collaboration on dental matters than facilities lacking such clinics. CONCLUSIONS: Our nationwide survey revealed that most dialysis facilities in Japan have neither an in-house dental department nor a collaborative relationship with a registered dental clinic. Registration of dental clinics appears to promote collaboration with dental facilities on a routine basis, which would be beneficial for oral health management in hemodialysis patients.

Preventive effect of Daiokanzoto (TJ-84) on 5-fluorouracil-induced human gingival cell death through the inhibition of reactive oxygen species production.

Daiokanzoto (TJ-84) is a traditional Japanese herbal medicine (Kampo formulation). While many Kampo formulations have been reported to regulate inflammation and immune responses in oral mucosa, there is no evidence to show that TJ-84 has beneficial effects on oral mucositis, a disease resulting from increased cell death induced by chemotherapeutic agents such as 5-fluorouracil (5-FU). In order to develop effective new therapeutic strategies for treating oral mucositis, we investigated (i) the mechanisms by which 5-FU induces the death of human gingival cells and (ii) the effects of TJ-84 on biological events induced by 5-FU. 5-FU-induced lactate dehydrogenase (LDH) release and pore formation in gingival cells (Sa3 cell line) resulted in cell death. Incubating the cells with 5-FU increased the expression of nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) and caspase-1. The cleavage of caspase-1 was observed in 5-FU-treated cells, which was followed by an increased secretion of interleukin (IL)-1ß. The inhibition of the NLRP3 pathway slightly decreased the effects of 5-FU on cell viability and LDH release, suggesting that NLRP3 may be in part involved in 5-FU-induced cell death. TJ-84 decreased 5-FU-induced LDH release and cell death and also significantly inhibited the depolarization of mitochondria and the up-regulation of 5-FU-induced reactive oxygen species (ROS) and nitric oxide (NO) production. The transcriptional factor, nuclear factor-κB (NF-κB) was not involved in the 5-FU-induced cell death in Sa3 cells. In conclusion, we provide evidence suggesting that the increase of ROS production in mitochondria, rather than NLRP3 activation, was considered to be associated with the cell death induced by 5-FU. The results also suggested that TJ-84 may attenuate 5-FU-induced cell death through the inhibition of mitochondrial ROS production.

The Kampo medicine Rokumigan possesses antibiofilm, anti-inflammatory, and wound healing properties.

Periodontal diseases, which are inflammatory diseases of bacterial origin affecting the tooth-supporting tissues, are characterized by inflammation and destruction of gingival connective tissue and alveolar bone, and may lead to tooth loss. The aim of the study was to investigate Rokumigan, a Kampo Japanese traditional medicine made of six different plants, for its capacity to prevent biofilm formation by Fusobacterium nucleatum, to inhibit interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion by mucosal cells, and to promote wound healing in a fibroblast model. Using a microplate colorimetric assay, Rokumigan prevented biofilm formation by F. nucleatum, while it had no effect on bacterial growth. Rokumigan inhibited IL-6 secretion in both epithelial cells and fibroblasts stimulated with lipopolysaccharide. However, it caused no significant inhibition of IL-8 secretion by both cell types. Rokumigan significantly increased proliferation and migration of gingival fibroblasts in a wound healing assay. In conclusion, the Kampo formulation Rokumigan, through suppression of biofilm formation by F. nucleatum, inhibition of IL-6 secretion by gingival epithelial cells and fibroblasts, and promotion of wound healing in a fibroblast model, may have potential application for periodontal diseases.