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The effects of nimesulide, a selective inhibitor of cyclo-oxygenase-2 (COX-2) on azoxymethane (AOM)-induced colon carcinogenesis were investigated in mice. AOM at a dose of 10 mg/kg body wt was administered to male ICR mice once a week for 6 weeks. The animals were fed on AIN-76A powder diet containing nimesulide at doses of 200 or 400 p.p.m., starting the day before the first carcinogen treatment until the end of the experiment, at week 30. Administration of nimesulide reduced the incidence of colon carcinomas to 32 and 25% for the AOM + 200 and 400 p.p.m. nimesulide groups, respectively, compared with the AOM + basal diet group (50%). Multiplicities of colon carcinomas in the 200 and 400 p.p.m nimesulide-treated groups were 0.70 ± 0.28 and 0.35 ± 0.11, respectively, being significantly smaller than the AOM alone value (1.79 ± 0.47). The sizes of the colon carcinomas in the nimesulide-treated groups were also decreased. No significant influence on liver and lung tumor development was apparent. Thus, nimesulide exerted a suppressive effect on AOM-induced colon carcinogenesis in mice. [ABSTRACT FROM PUBLISHER]

The effects of intragastric gavage administration of docosahexaenoic acid (DNA) , a major component of fish oil, on azoxymethane (AOM)-induced colon carcinogenesis in rats was investigated. Male F344 rats were treated with 15 mg/kg body wt of AOM once a week, for two weeks. The animals were given either 1 ml of DHA or water intragastrically 5 times a week, starting the day before the first carcinogen treatment. The numbers of AOM-induced aberrant crypt foci in the rats given DHA were 76% and 62% of the control values, at 4 and 12 weeks, respectively. After 36 weeks of DHA treatment, colon tumors were counted and examined histologically. The blood plasma levels of prostaglandin E2 (PGE2) and polyunsaturated fatty acids were also quantified. The incidences of colon cancer did not differ, being 96% and 92% in the AOM and AOM+DHA groups, respectively. Colon cancer multiplicity was, however, significantly decreased by the DHA treatment; 3.65 +/- 2.18 in the AOM group and 2.41 +/- 1.58 in the AOM+DHA group (P <0.01). Notably, the numbers of moderately differentiated adenocarcinomas in the middle and distal colon in the DHA-treated group were lower than in the AOM group. The levels of PGE2 and arachidonic acid in the blood plasma of DHA-treated rats were also significantly lower than in the AOM group. These results suggest that DHA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting the arachidonic cascade. [ABSTRACT FROM PUBLISHER]

Recent genome-wide association study (GWAS) and gene expression analyses have revealed that single nucleotide polymorphisms (SNPs) associated with complex diseases such as schizophrenia are significantly more likely to be associated with expression quantitative trait loci (eQTL). The interleukin-1β (IL1B) gene has been strongly implicated in the susceptibility to schizophrenia. In order to test this association, we selected five tag SNPs in the eQTL of the IL1B gene and conducted a case-control study using two independent samples. The first sample comprised 528 schizophrenic patients and 709 controls and the second sample comprised 576 schizophrenic patients and 768 controls. We identified two SNPs and several haplotypes as being significantly associated with schizophrenia. Previous reports indicated that one major haplotype that was protective against schizophrenia reduced IL1B transcription, while two risk haplotypes for schizophrenia enhanced IL1B transcription. Therefore, we measured IL1B mRNA expression in PAXgene-stabilized whole blood from 40 schizophrenic patients and 40 controls to explore the possibility of using five tag SNPs as schizophrenic trait markers. A multiple regression analysis taking confounding factors into account revealed that the T allele of rs4848306 SNP, which is a protective allele for schizophrenia, predicted reduced change in IL1B mRNA expression, regardless of phenotype. Our results appear to support the previous hypothesis that IL1B contributes to the genetic risk of schizophrenia and warrant further research on the association of eQTL SNPs with schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with impaired masticatory function tend to prefer soft foods, which results in decreased masticatory muscle activity. This study examined the association between the oral condition (number of teeth, occlusal force, and occlusal contact area) and dietary hardness using a daily dietary questionnaire., Methods: This cross-sectional study evaluated 1841 participants aged 69-71 and 79-81 years. Registered dentists examined the number of teeth, occlusal force, and occlusal contact area. Dietary hardness was defined as the estimated masticatory muscle activity required for a habitual diet. Habitual diet during the preceding month was assessed using a brief self-administered diet history questionnaire. Confounding factors, such as age, sex, socioeconomic status, smoking habits, history of chronic diseases (hypertension, hyperlipidemia, and diabetes), and cognitive function were also evaluated. Multivariate linear regression analyses were performed to assess the association between dietary hardness and each oral condition., Results: Occlusal force (standardized regression coefficients [β]=0.08, P < 0.01) and occlusal contact area (β=0.06, P < 0.01) were significantly associated with dietary hardness after adjusting for the confounding factors. Number of teeth was not significantly associated with dietary hardness. In addition, the associations between dietary hardness, sex, and a history of diabetes were stronger than those between dietary hardness and oral factors., Conclusions: Occlusal force and contact area were significantly associated with dietary hardness as estimated from the masticatory muscle activity using a daily diet questionnaire.

Background: Frailty increases the risk of negative health-related events, such as falls, disability, hospitalizations, and death. Although the association between oral health and physical frailty is well established, the relationship between oral health and psychological frailty has not yet been investigated. Therefore, we conducted a cross-sectional study to examine the association between maximal occlusal force and psychological frailty in Japanese community-dwelling older adults., Methods: Psychological frailty was defined as a World Health Organization-5 scale (WHO-5) score of <13, cognitive and functional status was defined as a Japanese version of the Montreal Cognitive Assessment (MoCA-J) score of <23, and psychological robustness was defined as a WHO-5 score of ≥13 and a MoCA-J score of ≥23. We used a cross-sectional study design to measure maximal occlusal force in 1810 participants, and examined the following factors relevant to psychological frailty: educational level, financial status, living situation, history of chronic diseases, handgrip strength, and instrumental activities of daily living. We used propensity score matching to match the psychological frailty and psychological robustness groups according to demographic and confounding factors. This process, resulted in 344 participants, of whom 172 were in the psychological frailty group and 172 were in the psychological robustness group. In the matched cohort, differences between groups with and without psychological frailty were compared using generalized estimating equations for maximal occlusal force after adjusting for the number of teeth., Results: After controlling for potential confounding factors of frailty, the psychological frailty group showed lower maximal occlusal force compared with the psychological robustness group (unstandardized regression coefficients = -72.7, 95% confidence interval: -126.3 to -19.1)., Conclusions: Maximal occlusal force was associated with a reduced prevalence of psychological frailty among Japanese community-dwelling older adults participating in our study., (© 2023 The American Geriatrics Society.)

Objectives: The aim of this cohort study among community-dwelling older adults aged over 70 years was to investigate the influence of occlusal support on tooth loss, and to determine predictive factors for tooth loss for each occlusal support category using multilevel analyses., Methods: Participants were 812 older adults who completed the baseline survey and the follow-up survey 6 years later. The Eichner index was used to evaluate occlusal support status. A generalized estimating equation (GEE) logistic regression analysis was used to examine the influence of occlusal support status on tooth loss while adjusting for various factors at individual and tooth levels. Similar analyses were separately performed in each Eichner class to determine predictive factors for tooth loss., Results: The GEE showed that a decline in occlusal support increased the risk of tooth loss (Eichner A: reference category, Eichner B: odds ratio (OR) = 1.96, p < 0.001, Eichner C: OR = 3.04, p < 0.001). Stratified analysis showed that deeper periodontal pockets and abutment teeth for fixed partial dentures were significantly associated with tooth loss, regardless of occlusal support. In Eichner A, the presence of an opposing tooth was advantageous in protecting the tooth, and a missing adjacent tooth was not significantly associated with tooth loss. An opposing tooth was associated with the risk of tooth loss in Eichner B, and a missing adjacent tooth was significantly associated with tooth loss in Eichner B and C., Conclusions: A decline in occlusal support accelerated tooth loss. Predictive factors for tooth loss varied depending on occlusal support status., Clinical Significance: Occlusal support is an important factor in preventing tooth loss. Dentition conditions such as missing adjacent teeth and the presence of opposing teeth increase the risk of tooth loss in participants with poor occlusal support. Dental personnel need to carefully examine dentition conditions to assess the risk of occlusal collapse., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Many physical functions decline with aging, but it is not known whether oral functions vary according to sex or decline with aging, as it occurs with physical functions. The present study aimed to examine the association of sex, age, and elapsed years with occlusal force and tongue pressure using a generalized linear mixed-effect model (GLMM) over a 3-year period among old-old Japanese adults., Methods: Participants were community-dwelling older adults who participated in a survey (June 2014-March 2017) and a follow-up survey (July 2017-December 2019) after 3 years (n = 951: 70-year group, n = 466; 80-year group, n = 391; 90-year group, n = 94). Dental examinations including the number of teeth, occlusal force, and tongue pressure were conducted, and a GLMM was used to estimate the association of sex, age, and elapsed years with occlusal force and tongue pressure, adjusting for the number of teeth., Results: The GLMM showed that occlusal force was significantly associated with sex (reference; male, non-standardized coefficient: B = -66.9 [female], p < 0.001), age (reference; 70-year group, B = -81.7 [80-year group], p < 0.001, B = -87.2 [90-year group], p < 0.001), and the number of teeth (B = 13.8, p < 0.001), but did not significantly decrease with elapsed years. Tongue pressure was significantly associated with sex (reference; male, B = -0.94 [female], p = 0.034) and age (reference; 70-year group, B = -1.78 [80-year group], p < 0.001, B = -5.47 [90-year group], p < 0.001). Tongue pressure decreased significantly with elapsed years (B = -0.82, p < 0.001)., Conclusions: These findings suggest that tongue pressure significantly decreased over time, but occlusal force did not. Tongue-related muscles may be more susceptible to aging than masticatory muscles., (© 2021 The American Geriatrics Society.)

Grip strength and walking speed are considered to be important indicators of physical frailty. However, no study has contemporaneously examined any association of multiple oral functions with grip strength and walking speed. The purpose of this study was to examine which oral functions are associated with muscle strength (grip strength), physical performance (walking speed) or both. The study participants were 511 community-dwelling people (254 men and 257 women) aged 77-81 years old. Six oral functions-oral wetness, occlusal force, tongue-lip motor function, tongue pressure, masticatory performance and swallowing function-were measured. Grip strength and walking speed were also measured. A partial correlation analysis, adjusted for gender, showed that occlusal force, tongue-lip motor function, masticatory performance and swallowing function were significantly associated with both grip strength and walking speed. In addition, tongue pressure was significantly associated with grip strength. A general linear model showed that tongue pressure and occlusal force were significantly associated with grip strength. Swallowing function and tongue-lip motor function were significantly associated with walking speed. It is suggested that there are different oral function measures for muscle strength and physical performance, and these oral function measures could be a useful proxy for physical frailty.

Aim: This work is aimed to create a strategy to improve the nurses' working environment., Background: As the working-age population is expected to decline in Japan, the maintenance of the nurse workforce is important. In order to create a strategy to improve the nurses' working environment, we studied the relationship among factors of organizational justice (procedural, distributive, and interactional justices), organizational citizenship behavior, job satisfaction, and ease of work., Methods: A cross-sectional, self-administered questionnaire was distributed to 969 nurses and 322 effective responses were analyzed (effective response rate 33.2%). The questionnaire contained demographic information, ease of work, and three scales for organizational justice, organizational citizenship behavior, and job satisfaction. The factor structure of the scales was studied using exploratory and confirmatory factor analysis. Structural equation modeling was used to investigate the relationship among measurements. The protocol was approved by the ethical committee of the author's university., Results: The final model showed a fair fit to the data (χ 2  = 1803.15, df = 1014, p < 0.001, comparative fit index = 0.907, root mean square error of approximation = 0.049). Interactional justice showed the most significant correlation to job satisfaction (r = 0.590). Job satisfaction and ease of work also showed a significant positive correlation (r = 0.696). Distributive justice had a slight negative indirect effect on job satisfaction, whereas procedural justice had no significant effect., Conclusion: In order to enhance job satisfaction/ease of work among Japanese nurses, improvement of interactional justice may be the best strategy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine any independent influence of occlusal force and of number of natural teeth on decline in body mass index (BMI) among older Japanese adults., Design: Longitudinal study over a 3- to 6-year period., Setting: Urban and rural area in Japan., Participants: Independently living Japanese adults aged 69-71 years and 79-81 years at baseline. This analysis excluded participants who were defined as underweight at baseline., Measurements: Information was collected on age, gender, occlusal force, the number of teeth, BMI, socioeconomic factors, medical history, the number of daily prescription medications, cognitive function, depressive symptoms, hand grip strength, and physical function. Maximal occlusal force was measured with a pressure-sensitive sheet. Nutritional status was assessed using BMI, and participants with BMI <21.5 were defined as underweight. Then, they were divided into two groups: a "BMI declined" group who were defined as underweight at either 3- or 6-year follow-up survey, and a "BMI maintained" group who were not defined as underweight at both follow-up surveys. Logistic generalized estimating equation (GEE) models were used to assess the effect of occlusal force and the number of teeth at baseline on decline in BMI over 3 or 6 years, after adjusting for possible covariates associated with nutritional status., Results: The final analysis included 704 participants. Eighty-six (12.2%) participants were classified into the BMI declined group. Logistic GEE models showed that the number of teeth was not significantly associated with decline in BMI. However, occlusal force was significantly associated with decline in BMI (odds ratio = 0.90, 95% confidence interval = 0.83-0.97) after adjusting for covariates., Conclusion: Participants with lower occlusal force were more likely to be in the BMI less than 21.5 kg/m 2 . The findings suggest that to prevent decline in oral function is important to maintain nutritional status., (© 2021 The American Geriatrics Society.)

The use of mesenchymal stem cell sheets is a promising strategy for skin regeneration. The injection of dissociated human amniotic fluid stem cells (hAFSCs) was recently found to accelerate cutaneous wound healing with reduced fibrotic scarring, similar to fetal wound healing. However, the use of hAFSCs in applications of cell sheet technology remains limited. The aim of this study was to determine the in vivo efficacy of in vitro-cultured hAFSC sheets in wound healing. The cell sheets were characterized by immunohistochemistry and RT-qPCR and grafted onto full-thickness wounds in BALB/c mice. The wound size was measured, and re-epithelialization, granulation tissue area, and collagen content of the regenerated wound were analyzed histologically. Although the hAFSC sheet contained abundant extracellular matrix molecules and expressed high levels of anti-fibrotic mediators, its grafting did not affect wound closure or the size of the granulation tissue area. In contrast, the organization of type I collagen bundles in the regenerated wound was markedly reduced, while the levels of type III collagen were increased after implantation of the hAFSC sheet. These results suggest that hAFSC sheets can exert anti-fibrotic properties without delaying wound closure., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Even in the context of modern medicine, infants with fetal and neonatal neurological diseases such as cerebral palsy and myelomeningocele suffer serious long-lasting impairment due to the irreversible neuronal damage. The promotion of neurologically intact survival in patients with perinatal intractable neurological diseases requires the development of novel strategies. One promising strategy involves the use of human amniotic fluid stem cells (hAFSCs), which have attracted much attention in recent years and are known to exert anti-inflammatory and neuroprotective effects. In recent years, the therapeutic effects of hAFSCs on fetal-neonatal neurological diseases have become evident as per intense research efforts by our group and others. Specifically, hAFSCs administered into the nasal cavity migrated to the brain and controlled local inflammation in a rodent model of neonatal hypoxic-ischemic encephalopathy. In contrast, hAFSCs administered intraperitoneally did not migrate to the brain; they rather formed spheroids in the abdominal cavity, resulting in the suppression of systemic inflammation (including in the brain) via the secretion of anti-inflammatory cytokines in concert with peritoneal macrophages in a rodent model of periventricular leukomalacia. Moreover, studies in a rat model of myelomeningocele suggested that hAFSCs administered in utero secreted hepatocyte growth factor and protected the exposed spinal cord during pregnancy. Importantly, autologous hAFSCs, whose use for fetal-neonatal treatment does not raise ethical issues, can be collected during pregnancy and prepared in sufficient numbers for therapeutic use. This article outlines the results of preclinical research on fetal stem cell therapy, mainly involving hAFSCs, in the context of perinatal neurological diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Despite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis., Methods: hAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis., Results: Prophylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways., Conclusions: Prophylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

Background: Given Japan's rapidly ageing society, an increasing number of elderly people live in their communities with mutual support after the death of their spouse. The purpose of this study is to clarify the relationship among independence of daily living, human relationships, and preparation for bereavement., Methods: An anonymous, self-administered questionnaire was given to 864 community-dwelling elderly people aged 65 and older who attended an Elderly Citizens' Welfare Study Group. A total of 404 responses (effective response ratio: 46.8%) were analyzed. Their mean ± SD age was 75.6 ± 5.1 years. The purpose of the questionnaire was to obtain demographic information as well as information about three scales: independence of daily living, human relationships, and preparation for bereavement. The factor structure of the scales was studied by using exploratory and confirmatory factor analysis. Structural equation modelling was used to investigate the relationship among independence of daily living, human relationships, and preparation for bereavement. This study's protocol was approved by the Ethics Committee of Okayama Prefectural University., Results: Factor analysis indicated a three-factor second-order factor model for independence of daily living and human relationships and a one-factor model for preparation for bereavement. Structural equation modelling showed that independence of daily living was significantly correlated with human relationships (r = 0.261, P < 0.001), and human relationships was significantly correlated with preparation for bereavement (r = 0.295, P < 0.001). There was no significant direct correlation between the independence of daily living and preparation for bereavement., Conclusions: Encouraging elderly people to form good human relationships may help their preparation for bereavement. Further studies are required to determine whether this actually attenuates difficulties after bereavement., (© 2020 Japanese Psychogeriatric Society.)

Purpose: Dementia is a growing health problem for countries with aging populations, but few effective dementia treatments are available. However, there is increasing interest in oral health as a modifiable risk factor in interventions to prevent cognitive decline. This study aimed to investigate the impact of oral health on the decline of cognitive function over 3 years among Japanese people aged 70 and 80 years., Methods: Participants (n = 860) were community-dwelling older adults who participated in baseline and follow-up surveys (at baseline: 69-71 years n = 423; 79-81 years, n = 437). Registered dentists examined the number of teeth, number of functional teeth, number of periodontal teeth, and occlusal force. The Japanese version of the Montreal Cognitive Assessment was used to evaluate cognitive function. We also evaluated socioeconomic factors, medical history, drinking and smoking habits, physical performance, genetic factors, and C-reactive protein concentration in blood. A generalized estimating equation (GEE) was used to examine how oral health at baseline influenced cognitive decline over 3 years., Results: The GEE showed that the number of teeth (non-standardized coefficient: B = 0.031, p = 0.022) and occlusal force (B = 0.103, p = 0.004) at baseline were associated with cognitive function at follow-up, even after adjusting for other risk factors. Furthermore, maintaining more teeth (B = 0.009, p = 0.004) and a stronger occlusal force (B = 0.020, p = 0.040) buffered cognitive decline., Conclusions: Number of teeth and occlusal force predict cognitive decline over 3 subsequent years in Japanese older adults aged 70 and 80 years., (Copyright © 2019 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Many older people lose their teeth. However, few studies have examined whether the number of remaining teeth or the amount of occlusal support is more important for tooth loss that occurs in older age after adjusting for systemic factors. The purpose of this study was to investigate comprehensively the factors related to tooth loss over a period of 6 years, including occlusal support in 70- and 80-year-old community-dwelling Japanese people., Methods: This cohort study included 296 participants in the 70-year-old group and 232 in the 80-year-old group. The number of teeth of all participants was recorded at baseline and after 6 years, and the participants were divided into two groups according to the number of teeth lost (0 or 4 or more). Occlusal support was classified into three groups based on posterior occlusal support. Mean probing pocket depth, tooth brushing habits, frequency of dental check-ups, education level, economic status and systemic factors (carotid atherosclerosis, hypertension, diabetes mellitus, dyslipidemia, cognitive function and smoking habits) were evaluated. Multiple logistic regression analysis was performed to investigate the relationship of tooth loss with occlusal support and systemic factors., Results: Logistic regression analysis revealed that mean probing pocket depth (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 2.70-12.04, P < .01) and posterior occlusal support (reference = Eichner class A; Eichner B1-3, OR = 4.33, 95% CI = 1.54-12.17, P < .01; Eichner B4 or C, OR = 6.16, 95% CI = 1.17-32.44, P = .03) were associated significantly with the loss of four or more teeth., Conclusions: This study revealed that age itself is not a predictor of multiple tooth loss in community-dwelling older Japanese people. Deep mean probing pocket depth and a lack of posterior occlusal support were significantly associated with the loss of four or more teeth., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs-based treatment for fetal MMC. hAFSCs were isolated as CD117-positive cells from the amniotic fluid of 15- to 17-week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC-treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC-treated group. Additionally, in lesions of the hAFSC-treated group, HGF expression was upregulated and HGF-positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170-1179., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Objective: To investigate the association between posterior occlusal support by residual teeth and the reduction in walking speed in 80-year-old Japanese adults using propensity score matching., Background Data Discussing the Present Status of the Field: Previous studies have demonstrated an association between oral status and motor function; however, most of these studies had a cross-sectional design., Material and Method: This study included 353 community-dwelling Japanese people aged 79-81 years. Low walking speed was defined as ≤0.8 m/s, and participants with a low walking speed at baseline were excluded. The participants were divided into two groups: with or without posterior occlusal support by residual teeth at baseline. Propensity score matching was used to reduce the effects of bias by matching participants with and without posterior occlusal support according to similar background factors at baseline. Conditional logistic regression was conducted to determine low walking speed at the 3-year follow-up, which included posterior occlusal support as an independent variable with matching data., Results: Before matching for posterior occlusal support, significant differences existed between the groups in terms of sex, years of education, height, weight and grip strength. However, after matching, there was no significant difference between the groups in any characteristic. Logistic regression analysis showed that posterior occlusal support is a significant variable (odds ratio = 1.88; P = 0.04) associated with reduced walking speed., Conclusion: Lack of posterior occlusal support at baseline independently predicted the incidence of reduced walking speed over 3 years., (© 2019 Gerodontology Association and John Wiley & Sons Ltd.)

Objectives: Oral tactile perception is important for better mastication, appetite, and enjoyment of food. However, previous investigations have not utilized comprehensible variables thought to have negative effect on oral perception, including aging, denture wearing, and cognitive function. The aim of this study was to elucidate the impact of cognitive function on oral perception in independently living older individuals., Materials and Methods: The study sample was comprised of 987 participants (466 males, 521 females; age 69-71 years). Oral examinations, assessments of cognitive function in preclinical level by Montreal Cognitive Assessment (MoCA)-J, and determination of oral stereognostic ability as an indicator of oral perception were performed. Related variables were selected by univariate analyses; then, multivariate logistic regression model analysis was conducted., Results: Univariate analyses revealed that number of teeth, removable dentures usage, and cognitive function respectively had a significant relationship with stereognostic score. Next, the subjects were classified into good and poor perception groups (lowest 17.4%) according to oral stereognostic ability. Logistic regression analysis revealed that lower cognitive function was significantly associated with poor oral perception (OR = 0.934, p = 0.017) after controlling for other variables., Conclusions: Cognitive decline even in preclinical stage was associated with reduced oral perception after controlling for gender, tooth number and denture use in independent living older people., Clinical Relevance: This study suggested that preclinical level of change in cognitive function affected oral perception. Dental practitioners and caregivers may need to pay attention to reduced oral perception among older people even if they do not have trouble in daily life.

Adult wound healing can result in fibrotic scarring (FS) characterized by excess expression of myofibroblasts and increased type I/type III collagen expression. In contrast, fetal wound healing results in complete regeneration without FS, and the mechanism remains unclear. Amniotic fluid cells could contribute to scar-free wound healing, but the effects of human amniotic fluid cells are not well characterized. Here, we determined the effect of human amniotic fluid stem cells (hAFS) on FS during wound healing. Human amniotic fluid was obtained by amniocentesis at 15-17 weeks of gestation. CD117-positive cells were isolated and defined as hAFS. hAFS (1 × 10 6 ) suspended in PBS or cell-free PBS were injected around wounds created in the dorsal region of BALB/c mice. Wound size was macroscopically measured, and re-epithelialization in the epidermis, granulation tissue area in the dermis and collagen contents in the regenerated wound were histologically analyzed. The ability of hAFS to engraft in the wound was assessed by tracking hAFS labeled with PKH-26. hAFS fulfilled the minimal criteria for mesenchymal stem cells. hAFS injection into the wound accelerated wound closure via enhancement of re-epithelialization with less FS. The process was characterized by lower numbers of myofibroblasts and higher expression of type III collagen. Finally, transplanted hAFS were clearly observed in the dermis until day 7 implying that hAFS worked in a paracrine manner. hAFS can function in a paracrine manner to accelerate cutaneous wound healing, producing less FS, a process resembling fetal wound healing.

Background: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE., Methods: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate-buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract., Results: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract., Conclusion: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.

Purpose: Oral stereognostic ability (OSA) is a useful indicator of oral perception to recognize food characteristics during mastication. Previous studies have shown associations between dietary intake and oral health status, such as taste perception. However, the effect of oral sensory ability on dietary intake is unclear. The purpose of this study was to investigate the association between oral sensory ability and dietary intake in older Japanese complete denture wearers., Methods: This cross-sectional study included 164 participants aged 69-71 or 79-81years old, wearing both maxillary and mandibular complete dentures. OSA test was used to evaluate oral tactile perception. Diet during the preceding month was assessed using a self-administered diet history questionnaire. Multivariable linear regression analysis was conducted to assess the association between OSA score and food and nutrient intake after adjusting for age, sex, socioeconomic factors, and occlusal force., Results: The bivariate analysis showed that OSA score was significantly and positively correlated with intake of green and yellow vegetables and negatively correlated with intake of cereals among examined foods. OSA score was also positively correlated with intake of vitamins A, B 2 , and C and α-tocopherol (as a substitute for vitamin E) among examined nutrients. After adjusting for age, sex, socioeconomic factors, and occlusal force, OSA score remained significantly associated with intake of green and yellow vegetables and α-tocopherol., Conclusions: OSA was significantly associated with intake of green and yellow vegetables in older complete denture wearers., (Copyright © 2018 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.)

Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.

Aim: Previous studies have reported significant associations between tooth loss or periodontal status and cognitive function; however, animal experimental studies have shown that occlusion might be a more important factor in cognitive decline. The purpose of the present study was to investigate the influence of a lack of posterior occlusal support by residual teeth on the decline of cognitive function over a 3-year period among 80-year-old Japanese people., Methods: Participants were community-dwelling older adults (n = 515, age 79-81 years). Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment. At baseline, participants were divided into two groups: those with and without posterior occlusal support. Participants whose Japanese version of the Montreal Cognitive Assessment score decreased by ≥3 points over the 3-year period were defined as the declined group. Logistic regression was carried out for the decline in Japanese version of the Montreal Cognitive Assessment scores, including dental status and possible risk factors as independent variables., Results: More participants without posterior occlusal support tended to be in the cognitive decline group (49.4%) than in the maintained group (38.5%; χ 2 -test, P = 0.02). Logistic regression analysis showed that a lack of posterior occlusal support was a significant variable (odds ratio 1.55, P = 0.03) for cognitive decline, even after adjusting for other risk factors. However, the number of teeth or mean periodontal pocket depth was not significantly correlated with cognitive decline., Conclusions: The present findings suggest that a lack of posterior occlusal support predicted the incidence of cognitive decline, even after adjusting for possible risk factors in community-dwelling old-old people. Geriatr Gerontol Int 2018; 18: 1439-1446., (© 2018 Japan Geriatrics Society.)

Objective: The purpose of this study was to elucidate the associations between muscle strength and several oral functions in a large cohort of community-dwelling, 82- to 84-year-old community-dwelling Japanese people., Background Data Discussing the Present Status of the Field: Several studies have examined the relationships between physical performance and oral functions. However, no studies have investigated the associations of muscle strength with various objectively evaluated oral functional parameters in a large cohort of very old adults., Materials and Methods: This study included 809 community-dwelling Japanese people (407 men and 402 women) aged 82-84 years. The oral functions examined were the maximal occlusal force, masticatory performance, stimulated salivary flow rate, repetitive saliva-swallowing test (RSST) score, tongue pressure and mouth-opening distance. Handgrip strength was measured, and its correlations with oral functions were assessed. Multiple linear and logistic regression analyses were performed to investigate the relationships between oral functions and handgrip strength., Results: Multivariate analysis revealed that handgrip strength was correlated with not only the maximal occlusal force, masticatory performance and tongue pressure but also the RSST score and mouth-opening distance after adjustment for sex, number of teeth, use of removable denture, periodontal condition, instrumental activities of daily living, body mass index. When we examine the elderly people whose handgrip strength is declining, we should predict that their various oral functions may be declining., Conclusion: Handgrip strength was related to various oral functions after adjustment for the number of teeth in this population of community-dwelling 82- to 84-year-old Japanese., (© 2018 Gerodontology Association and John Wiley & Sons Ltd.)

Background: Growing evidence suggests that oral health may be an important factor associated with cognitive function in aged populations. However, many previous studies on this topic used insensitive oral indicators or did not include certain essential covariates. Thus, we examined the association between occlusal force and cognitive function in a large sample of older adults, controlling for dietary intake, vascular risk factors, inflammatory biomarkers, depression, and genetic factors., Methods: In this cross-sectional study of older community-dwelling Japanese adults, we examined data collected from 994 persons aged 70 years and 968 persons aged 80 years. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were evaluated according to the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between MoCA-J scores and occlusal force were investigated via bivariate and multivariate analyses., Results: Education level, financial status, depression score, and intake of green and yellow vegetables, as well as number of teeth and occlusal force, were significantly correlated with MoCA-J scores in both age groups. Among individuals aged 80 years, CRP and periodontal status were weakly but significantly associated with MoCA-J score. After controlling for all significant variables via bivariate analyses, the correlation between maximal occlusal force and cognitive function persisted. A path analysis confirmed the hypothesis that cognitive function is associated with occlusal force directly as well as indirectly via food intake., Conclusions: After controlling for possible factors, maximal occlusal force was positively associated with cognitive function directly as well as indirectly through dietary intake.

Objective: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT)., Design: Retrospective cohort study., Setting: University hospital., Population: A total of 33 deliveries after 22 weeks' gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016., Methods: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver-operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth., Main Outcome Measures: Preterm birth before 34 weeks' gestation., Results: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75)., Conclusions: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT., Tweetable Abstract: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy., (© 2017 Royal College of Obstetricians and Gynaecologists.)

A mobile phone intervention was developed and tested with 30 psychiatric outpatients with mental illness, who had high ideation for suicide. The intervention involved promoting help-seeking behaviors by sending text messages, including information about social welfare services and reminders about medical appointments, for 6 months. After the intervention period, the number of participants who used social services significantly increased, and more than 80% of participants reported that the text messaging service was helpful and useful. Compared to baseline, participants' self-harming behaviors decreased and the attending psychiatrists rated their suicide ideation as weaker. This is the first intervention study to promote psychiatric patients' help-seeking using text messaging, and although it was not a randomized controlled trial, this intervention has practical value and may lead to the prevention of suicide., (Copyright 2016, SLACK Incorporated.)

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.

Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

A pharmaceutical grade Japanese traditional medicine, daikenchuto (TU-100), consisting of Japanese pepper, processed ginger, and ginseng, has been widely used for various intestinal disorders in Japan and now under development as a new therapeutic drug in the US. It is suggested that TU-100 ingredients exert pharmacological effects on intestines via two routes, from the luminal side before absorption and the peripheral blood stream after absorption. Therefore, in order to fully understand the pharmacological actions of TU-100, it is critically important to know the intraluminal amounts and forms of ingested TU-100 ingredients. In the present study, after administrating TU-100 to rats, the concentrations of TU-100 ingredients and their conjugates in the peripheral and portal blood and ileal contents were determined by LC-MS/MS. Next, TU-100 was administered to patients with ileostomy bags, but whose small intestines are diagnosed as healthy, and the ingredients/conjugates in the ileal effluent were analyzed. The results suggest that: (1) Pepper ingredients hydroxysanshools are rapidly absorbed and enter systemic circulation, (2) Ginseng ingredients ginsenosides are transported to the colon with the least absorption, (3) Ginger ingredients gingerols are absorbed and some conjugated in the small intestine and transported via the portal vein. While only a small amount of gingerols/gingerol conjugates enter systemic circulation, considerable amounts reappear in the small intestine. Thus, the effect of TU-100 on the intestines is believed to be a composite of multiple actions by multiple compounds supplied via multiple routes.

Background: Rikkunshito, a traditional Japanese (Kampo) medicine, has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux. This study investigated the exposure and pharmacokinetics of the ingredients of rikkunshito in healthy volunteers., Methods and Results: First, an exploratory nonrandomized, open-label, one-period, noncrossover study using four healthy Japanese volunteers to detect 32 typical ingredients of rikkunshito in plasma and urine. As a result, 18 or 21 of 32 ingredients was detected in plasma or urine samples after oral administration of rikkunshito (7.5 g/day). Furthermore, a randomized, open-label, three-arm, three-period, crossover study using 21 subjects was conducted to determine the amounts of exposure and pharmacokinetic parameters of nine ingredients derived from rikkunshito (atractylodin, atractylodin carboxylic acid, pachymic acid, 3,3',4',5,6,7,8-heptamethoxyflavone, naringenin, nobiletin, liquiritigenin, isoliquiritigenin, and 18β-glycyrrhetinic acid) after oral administration of rikkunshito at three different doses (2.5, 5.0, or 7.5 g/day) during each period. The pharmacokinetic profiles of the nine ingredients in plasma were characterized. The geometric means (95% confidence interval) for the Cmax of the ingredients at a dose of 7.5 g were 1570 (1210-2040), 14,300 (12,200-16,800), 91.0 (71.8-115), 105 (75.6-144), 1150 (802-1650), 35.9 (24.6-52.5), 800 (672-952), 42.8 (30.4-60.3), and 55,600 (39,600-78,100) pg/mL, respectively, and for the AUC0-last were 1760 (1290-2390), 12700 (11,100-14,600), 1210 (882-1650), 225 (157-322), 4630 (2930-7320), 35.7 (20.4-62.7), 4040 (3260-5010), 122 (88.2-168), and 832,000 (628,000-1,100,000) pg·h/mL respectively., Conclusions: We identified the ingredients of rikkunshito that are absorbed in humans. Furthermore, we determined the pharmacokinetics of nine ingredients derived from rikkunshito. This information will be useful for elucidating the pharmacological effects of rikkunshito., Trial Registration: Japan Pharmaceutical Information Center #CTI-121801 and -142522.

Shakuyakukanzoto (SKT) is a kampo medicine composed of equal proportions of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix). A double-blind study reported that SKT significantly ameliorated painful muscle cramp in cirrhosis patients without the typical severe side effects of muscle weakness and central nervous system (CNS) depression. Previous basic studies reported that SKT and its active components induced relaxation by a direct action on skeletal muscle and that SKT did not depress CNS functions; however, why SKT has a lower incidence of muscle weakness remains unknown. In the present study, we investigated which components are absorbed into the blood of rats after a single oral administration of SKT to identify the active components of SKT. We also investigated the effects of SKT and its components on the twitch contraction induced by physiological Ca(2+) release. Our study demonstrated that SKT and five G. radix isolates, which are responsible for the antispasmodic effect of SKT, did not inhibit the twitch contraction in contrast to dantrolene sodium, a direct-acting peripheral muscle relaxant, indicating that the mechanisms of muscle contraction of SKT and dantrolene in skeletal muscle differ. These findings suggest that SKT does not reduce the contractile force in skeletal muscle under physiological conditions, i.e., SKT may have a low risk of causing muscle weakness in clinical use. Considering that most muscle relaxants and anticonvulsants cause various harmful side effects such as weakness and CNS depression, SKT appears to have a benign safety profile.

Oral mucositis (OM) is a common and painful complication of radiotherapy for head and neck cancer. Hangeshashinto (HST), a Japanese traditional medicine, is known to alleviate radiotherapy- and/or chemotherapy-induced OM; however, the detailed mechanism has not yet been clarified. The aim of the present study was to clarify the details of the antioxidative functions of HST against reactive oxygen species (ROS) produced by radiation. The hydroxyl radical (•OH)-scavenging ability and the reduction ability was simultaneously measured using a modified electron paramagnetic resonance (EPR) spin-trapping method. The superoxide (O(2) (•-))-scavenging ability was estimated by an EPR redox probing method. Water suspensions of powdered HST and of its seven constitutive crude drugs were tested. In addition, some of the main water-soluble ingredients of the crude drugs were also tested. HST was found to scavenge both •OH and O(2) (•-). Furthermore, HST was observed to reduce relatively stable nitroxyl radicals. Glycyrrhizae Radix (kanzo), Ginseng Radix (ninjin), Zizyphi Fructus (taiso) and glycyrrhizin (an ingredient of kanzo) were all found to be relatively good •OH scavengers. Scutellariae Radix (ogon) and Coptidis Rhizoma (oren) demonstrated reducing ability. In addition, acteoside and berberine chloride, which are water-soluble ingredients of ogon and oren, respectively, also demonstrated reducing ability. Oren exhibited oxidative ability at higher concentrations, which may have a function in maintaining catalytic redox action. The antioxidative function of HST probably worked via a balance of scavenging ROS, reducing stable free radicals, and some minor oxidizing activities., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Oral mucositis (OM) in cancer patients induced by chemotherapy or radiotherapy has a significant impact on quality of life, and causes considerable morbidity. Oral microorganisms are likely to intensify the inflammatory process and aggravate the formation of ulcers. Hangeshashinto (HST), a Japanese kampo medicine, has been reported to be effective when used as a gargle for the treatment of OM. To clarify the effects of HST on oral microorganisms, we assessed its antimicrobial activity against 27 microbial species, including 19 oral bacteria and one fungus. HST extract inhibited the growth of Gram-negative bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella melaninogenica, Tannerella forsythia, Treponema denticola, and Porphyromonas asaccharolytica, though inhibitory effects were less pronounced for Gram-positive bacteria and the fungal strain. We then investigated the effects of antibacterial activities on 15 purified ingredients of HST and determined that baicalein, berberine, coptisine, [6]-shogaol, and homogentisic acid actively inhibited the growth of these bacteria. These findings showed that HST inhibits the growth of specific Gram-negative periodontopathogenic bacteria, which are significant pathogens in OM, without disturbing the normal oral flora. Our data suggest that HST may be a useful treatment for OM in patients undergoing anticancer treatment.