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The surface pre-reacted glass ionomer (S-PRG) filler is a type of bioactive functional glass that releases six different ions. This study examined the effects of the S-PRG filler eluate on Streptococcus mutans in the presence of sucrose. In a solution containing S. mutans , the concentrations of BO 3 3- , Al 3+ , Sr 2+ , and F - were significantly higher in the presence of the S-PRG filler eluate than in its absence ( p < 0.001). The concentrations of these ions further increased in the presence of sucrose. Additionally, the S-PRG filler eluate significantly reduced glucan formation by S. mutans ( p < 0.001) and significantly increased the pH of the bacterial suspension ( p < 0.001). Bioinformatic analyses revealed that the S-PRG filler eluate downregulated genes involved in purine biosynthesis (purC, purF, purL, purM, and purN) and upregulated genes involved in osmotic pressure (opuAa and opuAb). At a low pH (5.0), the S-PRG filler eluate completely inhibited the growth of S. mutans in the presence of sucrose and significantly increased the osmotic pressure of the bacterial suspension compared with the control ( p < 0.001). These findings suggest that ions released from the S-PRG filler induce gene expression changes and exert an inhibitory effect on S. mutans in the presence of sucrose.

Multiple myeloma (MM) is an incurable B-cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL-18 and M-CSF levels showed significantly shorter progression-free survival and overall survival (OS). In contrast, patients with high PDGF-BB levels had longer survival. Moreover, low levels of G-CSF, IL-7, IL-8, and SDF-1α were associated with shorter OS after Ld therapy. During Ld therapy, pro-inflammatory cytokines such as IL-2Rα, IL-18, and TNF-α were decreased, while IFN-γ was increased. IL-4 and IL-6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Chemotherapy is a common treatment for pediatric cancer. Although life prognosis is improving because of advances in medical science, it is important to deal with late effects such as dental abnormalities. We investigated the association between dental abnormalities and chemotherapy by age and tooth type. Methods: Among the 568 patients referred to the pediatric dentistry department of our hospital, we selected 32 patients (21 male and 11 female) who received chemotherapy between the ages of 0 and 6 and underwent panoramic examination after the age of 7. We recorded the age of chemotherapy commencement, diagnosis of systemic disease, and dental abnormalities such as congenital absence, microdonts, and short-rooted teeth. Results: Almost half of the patients had dental abnormalities such as congenital absence, microdonts, and short-rooted teeth, but there were no significant differences in the incidence of these abnormalities by age. When we analyzed the incidence of abnormal teeth by tooth type, the incidence of congenital absence was significantly higher in premolars (5.5%) and second molars (3.9%) than in incisor or canine or 1st molar (0.4%) ( p < 0.01). The incidence of microdonts was significantly higher in premolars (3.9%) than in incisor or canine or 1st molar (0.2%) and second molars (0.0%) ( p < 0.05). Conclusions: Patients who received chemotherapy had a high prevalence of dental abnormalities, and the incidence of abnormalities varied by tooth type. It is important to maintain long-term oral care for patients who have undergone chemotherapy even after the treatment is completed.

Human endogenous retroviruses (HERVs) are retrotransposons that infect human germline cells and occupy 5-8% of the human genome. Their expression, though inhibited by mutation, deletion, and epigenetic mechanisms under normal conditions, is associated with diseases including cancer. This study aimed to clarify the association between HERVs and multiple myeloma (MM) progression. We found that HERV-K envelope (env) and long-term repeat (LTR) expression was statistically significantly higher within plasma cells in MM than in monoclonal gammopathy of undetermined significance or controls. HERV-K env knockdown increased proliferation in the MM.1S cell line and decreased the expression of the tumor suppressor genes TP53 and CDKN1A. TP53 and CDKN1A were highly expressed in MM, and their expression was correlated with HERV-K expression. HERV-K knockdown reduced apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3F, 3G, and 3H expression by 10-20% in MM.1S cells. The anti-retroviral agents nevirapine and nelfinavir suppressed proliferation and increased HERV-K expression in MM cell lines. Our results suggest that HERV-K is involved in MM progression, but its role is likely to go beyond promoting cell proliferation. Clarifying the role of HERV-K in MM will lead to the discovery of novel treatment strategies and supply new insights into MM pathogenesis., (© 2022. Japanese Society of Hematology.)

Background: Although dental radiography is a valuable tool for age estimation in forensic anthropology and odontology, very limited radiological data are available regarding tooth development in healthy newborn babies during the first month of life., Aim: This study aimed to describe the radiological findings of tooth development in babies aged 0 days to 1 month., Design: We analyzed the postmortem findings of five newborn babies with no known natural cause of death who had undergone autopsy, computed tomography (CT), and dental radiography. We estimated the gestational age for the babies aged 0 days and analyzed the condition of mandibular symphysis, existence of tooth germs, and presence or absence of calcification of the first permanent molars of all the babies., Results: The calcified form of 20 deciduous teeth, tooth germs of the permanent upper and lower first molars, and non-calcified mandibular symphysis were observed in each case. However, calcification of the first permanent molar was observed in only two 1-month-old babies., Conclusion: The dental radiographic findings and anthropometric measurements of non-skeletonized, non-mummified term babies confirmed calcification of all the deciduous teeth and the first permanent molar at the age of 0 days and 1 month, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays. TIMP1 mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging. TIMP1 mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway.

Background and Objectives: Gastrectomy causes vitamin B-12 deficiency since vitamin B-12 requires gastric acid and intrinsic factor for its absorption. Vitamin B-12 deficiency is considered to develop years after gastrectomy because of large hepatic storage. However, most gastric cancer develops after long-standing atrophic gastritis with vitamin B-12 malabsorption., Methods and Study Design: We have investigated vita-min B-12 status in 22 patients before gastrectomy and 53 patients after gastrectomy due to gastric cancer, also with consideration on post-gastrectomy anemia., Results: Blood vitamin B-12, folic acid, homocysteine concentrations, parameters of anemia, and dietary intake were evaluated. Percentage of patients with severe vitamin B-12 deficiency (serum vitamin B-12 < 150 pmol/L), vitamin B-12 deficiency (150 pmol/L to < 258 pmol/L) was 19.0 %, and 52.4 % respectively in patients gastrectomized within three years. Before gastrectomy, three and seven patients exhibited severe deficiency and deficiency, respectively. In gastrectomized patients, plasma homocysteine concentration was inversely associated with serum vitamin B-12 concentration, and vitamin B-12 deficiency- and iron deficiency- anemia coexisted with their mean corpuscular volume within the reference range., Conclusions: Vitamin B-12 deficiency is prevalent in patients early after and before gastrectomy. Coexistence of vitamin B-12 and iron deficiency obscures the diagnosis of post-gastrectomy anemia, and necessitates the blood vitamin B-12 measurement.

Aim: In Cambodia, civil unrest has led to insufficient and inaccessible dental health services. Oral health education and awareness are lacking, thus childhood dental caries is highly prevalent. This study aimed to examine the effects of an oral health education programme for public primary school teachers on the pupils' oral health., Methods: Between 2011 and 2015, an oral health education workshop was presented annually to primary school educators employed at a public school in Siem Reap, Cambodia. Oral screenings of 2,637 pupils (grades 1-6; subdivided between the lower 1-3 and upper 4-6 grades) were undertaken and the prevalence of dental caries, mean number of DFT, and mean percentage of DFT rate were calculated., Conclusion: Despite the persistently high prevalence of dental caries, the oral health status of the schoolchildren improved every year. Participation in the workshops may have improved the teachers' ability to provide oral healthcare instructions, leading to the reduced dental caries prevalence among pupils.

Purpose: The purpose of this repeated cross-sectional study was to investigate the prevalence and severity of oral hygiene conditions in Cambodian primary school children., Methods: Oral examinations were conducted on 2,020 school children (1st-6th grade) at a public primary school in Siem Reap, Cambodia from 2013 to 2015, focusing on plaque adhesion, gingiva, and dental calculus deposition. Data analysis was performed on 1,998 children without any missing data, and the chi-square test was used to compare the variables., Results: The prevalence of dental plaque adhesion in 2013, 2014, and 2015 was 93.6%, 93.7%, and 85.1%, respectively. The prevalence of gingivitis in 2013, 2014, and 2015 was 93.1%, 92.1%, and 88.8%, respectively. The prevalence of dental calculus deposition in 2013, 2014, and 2015 was 55.1%, 19.3%, and 34.7%, respectively. Significant differences were observed in all variables each year (P < 0.001)., Conclusion: The findings of this study suggest that oral hygiene conditions were poor in this population.

Photoacoustic (PA) technology can be used for non-invasive imaging of blood vessels. In this paper, we report on our prototype PA imaging system with a newly designed ultrasound sensor and its visualization performance of microvascular in animal. We fabricated an experimental system for animals using a high-frequency sensor. The system has two modes: still image mode by wide scanning and moving image mode by small rotation of sensor array. Optical test target, euthanized mice and rats, and live mice were used as objects. The results of optical test target showed that the spatial resolution was about two times higher than that of our conventional prototype. The image performance in vivo was evaluated in euthanized healthy mice and rats, allowing visualization of detailed blood vessels in the liver and kidneys. In tumor-bearing mice, different results of vascular induction were shown depending on the type of tumor and the method of transplantation. By utilizing the video imaging function, we were able to observe the movement of blood vessels around the tumor. We have demonstrated the feasibility of the system as a less invasive animal experimental device, as it can acquire vascular images in animals in a non-contrast and non-invasive manner.

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose [FL]), are associated with the formation of a Bifidobacterium -rich gut microbial community. Phylogenetic analysis revealed that FL transporters have diversified into two clades harboring four clusters within the Bifidobacterium genus, but the underpinning functional diversity associated with this divergence remains underexplored. In this study, we examined the HMO consumption phenotypes of two bifidobacterial species, Bifidobacterium catenulatum subsp. kashiwanohense and Bifidobacterium pseudocatenulatum, both of which possess FL-binding proteins that belong to phylogenetic clusters with unknown specificities. Growth assays, heterologous gene expression experiments, and HMO consumption analyses showed that the FL transporter type from B. catenulatum subsp. kashiwanohense JCM 15439 T conferred a novel HMO uptake pattern that includes complex fucosylated HMOs (lacto- N- fucopentaose II and lacto- N- difucohexaose I/II). Further genomic landscape analyses of FL transporter-positive bifidobacterial strains revealed that the H-antigen- or Lewis antigen-specific fucosidase gene(s) and FL transporter specificities were largely aligned. These results suggest that bifidobacteria have acquired FL transporters along with the corresponding gene sets necessary to utilize the imported HMOs. Our results provide insight into the species- and strain-dependent adaptation strategies of bifidobacteria in HMO-rich environments. IMPORTANCE The gut of breastfed infants is generally dominated by health-promoting bifidobacteria. Human milk oligosaccharides (HMOs) from breast milk selectively promote the growth of specific taxa such as bifidobacteria, thus forming an HMO-mediated host-microbe symbiosis. While the coevolution of humans and bifidobacteria has been proposed, the underpinning adaptive strategies employed by bifidobacteria require further research. Here, we analyzed the divergence of the critical fucosyllactose (FL) HMO transporter within Bifidobacterium . We have shown that the diversification of the solute-binding proteins of the FL transporter led to uptake specificities of fucosylated sugars ranging from simple trisaccharides to complex hexasaccharides. This transporter and the congruent acquisition of the necessary intracellular enzymes allow bifidobacteria to consume different types of HMOs in a predictable and strain-dependent manner. These findings explain the adaptation and proliferation of bifidobacteria in the competitive and HMO-rich infant gut environment and enable accurate specificity annotation of transporters from metagenomic data.

Background: Due to the COVID-19 pandemic, a state of emergency was declared in Japan and university classes were suspended, causing concern about the deterioration of the mental health of isolated students. This study aimed to understand students' mental health status during the COVID-19 pandemic and suggest measures to prevent depressive anxiety among them., Method: Undergraduate and graduate students at one national and two private universities in the Kansai region were surveyed. The Kessler Psychological Distress Scale-6 was used to assess the students' mental health. Questions were included to assess students' awareness of COVID-19 and changes in lifestyle habits, including drinking, smoking, gaming, and other addictive habits. The University of Tokyo Health Sociology's version of the Sense of Coherence Scale was used to assess the ability to cope with stressors., Results: More than 50% of undergraduate and graduate students felt more than mild depressive anxiety and approximately 11% felt severe depressive anxiety, indicating that anxiety about the future worsened the levels of depressive anxiety. Life with reversed day and night schedules was associated with the worsening of depressive anxiety levels, but a high sense of coherence was associated with decreased levels of depressive anxiety., Conclusion: COVID-19 pandemic triggered isolation which led to worsening the mental health of undergraduate and graduate students. Psychological support for lifestyle and a sense of coherence is necessary to prevent mental health deterioration among isolated students., Limitations: As we were unable to contact all students, the sample bias may affect interpretation of the data., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Author(s).)