The effect of extracellular calcium ion on gene expression of bone-related proteins in human pulp cells

Calcium hydroxide is often used for induction of reparative dentin formation in endodontic treatment. However, little is known about the mechanism by which calcium hydroxide works. The calcium ion (Ca2+) is an important regulator of cell functions. In this study, we examined the effect of extracellular Ca2+ on gene expression of bone-related proteins in human cultured pulp cells in serum-free conditions. A Ca2+ level elevated by 0.7 mM induced an increase in mRNA expression of osteopontin and bone morphogenetic protein (BMP)-2. However, mRNA levels of BMP-4 and alkaline phosphatase decreased under the elevated Ca2+ culture condition. The same concentration of additional magnesium ions had little effect on expressions of the examined bone-related protein mRNAs. These findings suggest that Ca2+ in Ca(OH)2 specifically modulates osteopontin and BMP-2 levels during calcification in pulp.     

Clinical significance of proteinuria determined with dipstick test,edema, and weekly weight gain ⩾500 g at antenatal visit

ObjectiveTo determine how urine dipstick test, edema, and/or excessive weight gain (EWG, defined as ?500 g/week) at antenatal visits predict significant proteinuria (defined as a protein-to-creatinine ratio [P/Cr, mg/mg] ?0.27) and preeclampsia.MethodsData from 3279 antenatal visits between 30 and 36 weeks of gestation were studied in 783 women with singleton pregnancies. In 24 preeclamptic pregnancies, data from 89 antenatal visits at and before diagnosis of preeclampsia were used. Spot P/Cr was determined in women with repeated positive dipstick test results in two successive antenatal visits or in those with a positive dipstick test result tested in the presence of hypertension.ResultsProteinuria on dipstick test, edema, and EWG appeared often in both women with and without preeclampsia; 66.7% vs. 27.7%, 83.3% vs. 44.1%, and 91.7% vs. 81.6%, respectively. However, repeated positive dipstick test results in two successive antenatal visits yielded sensitivity of 45.5%, specificity of 95.2%, and positive and negative predictive values of 30.0% and 97.4%, respectively, for detection of significant proteinuria and corresponding figures of 33.3%, 94.1%, 14.0%, and 98.0% for prediction of preeclampsia.ConclusionRepeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria.     

BMP9‐ID1 signaling promotes EpCAM‐positive cancer stem cell properties in hepatocellular carcinoma

The malignant nature of hepatocellular carcinoma (HCC) is closely related to the presence of cancer stem cells (CSCs). Bone morphologic protein 9 (BMP9), a member of the transforming growth factor‐beta (TGF‐β) superfamily, was recently reported to be involved in liver diseases including cancer. We aimed to elucidate the role of BMP9 signaling in HCC‐CSC properties and to assess the therapeutic effect of BMP receptor inhibitors in HCC. We have identified that high BMP9 expression in tumor tissues or serum from patients with HCC leads to poorer outcome. BMP9 promoted CSC properties in epithelial cell adhesion molecule (EpCAM)‐positive HCC subtype via enhancing inhibitor of DNA‐binding protein 1 (ID1) expression in vitro. Additionally, ID1 knockdown significantly repressed BMP9‐promoted HCC‐CSC properties by suppressing Wnt/β‐catenin signaling. Interestingly, cells treated with BMP receptor inhibitors {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 and LDN‐212854 blocked HCC‐CSC activation by inhibiting BMP9‐ID1 signaling, in contrast to cells treated with the TGF‐β receptor inhibitor galunisertib. Treatment with LDN‐212854 suppressed HCC tumor growth by repressing ID1 and EpCAM in vivo. Our study demonstrates the pivotal role of BMP9‐ID1 signaling in promoting HCC‐CSC properties and the therapeutic potential of BMP receptor inhibitors in treating EpCAM‐positive HCC. Therefore, targeting BMP9‐ID1 signaling could offer novel therapeutic options for patients with malignant HCC.     

Phenotypic Changes in Macrophage Activation in a Model of Nonalcoholic Fatty Liver Disease using Microminipigs

Aim: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders associated with metabolic syndrome, and its prevalence has been on the rise. The pathogenesis of NAFLD has not yet been sufficiently elucidated due to the multifactorial nature of the disease, although the activation of macrophages/Kupffer cells is considered to be involved. We previously reported an animal model of NAFLD using Microminipigs ^TM (µMPs) fed high-fat diets containing cholesterol with or without cholic acid. The aim of this study was to investigate the phenotypic changes of macrophages that occur during the development of NAFLD. Methods: Immunohistochemistry of macrophages, lymphocytes, and stellate cells was performed using liver samples, and the density of positive cells was analyzed. Results: The number of Iba-1-positive macrophages increased with increasing cholesterol content in the diet. The numbers of CD163-positive macrophages and CD204-positive macrophages also increased with increasing cholesterol content in the diet; however, the proportion of CD204-positive macrophages among Iba-1-positive macrophages was significantly reduced by cholic acid supplementation. Conclusion: The results suggest that lipid accumulation induced macrophage recruitment in swine livers, and that the number of M2-like macrophages increased at the early stage of NAFLD, while the number of M1-like macrophages increased at the late stage of NAFLD, resulting in a liver condition like non-alcoholic steatohepatitis. We provide evidence of the phenotypic changes that occur in macrophages during the development of NAFLD that has never been reported before using µMPs.     

Localization of tumour necrosis factor-alpha converting enzyme in normal human skin

The tumour necrosis factor (TNF)-alpha converting enzyme (TACE) is a metalloproteinase-disintegrin that releases soluble TNF-alpha from cells by cleaving within the extracellular domain of membrane-bound pro-TNF-alpha. TACE knockout mice display a range of epithelial abnormalities. However, the localization of TACE in normal human skin is unclear. In this study, we examined the expression of TACE in normal skin by immunohistochemical analysis. The expression of TACE was seen throughout all layers of the epidermis, the hair follicles, eccrine ducts and glands, and sebaceous glands. There was also staining of blood vessels in the dermis. In particular, TACE was localized predominantly in mast cells, suggesting that these cells are an important source of TNF-alpha.     

A case of subcorneal pustular dermatosis treated with tacalcitol (1alpha,24-dihydroxyvitamin D3)

We report a case of subcorneal pustular dermatosis (SPD) treated with tacalcitol (1alpha,24-Dihydroxyvitamin D3) ointment. A 77-year-old male had had asymptomatic, superficial, grouped pustules in annular patterns with mild background erythema for six years which affected his axillae and bilateral groin. A diagnosis of SPD was made. Topical vitamin D3 (tacalcitol) was applied to the lesion of SPD and its clinical effectiveness was assessed. Within one month, symptoms in the lesion treated with tacalcitol ointment started subsiding, and eventually only erythema remained. After three months, the region treated with tacalcitol ointment showed no relapse. We conclude that tacalcitol ointment is effective for SPD in some case.     

Dermatomyositis and pregnancy. Case report and review of the literature.

Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well.     

Evaluation of occlusal status of Japanese adults based on functional tooth units

ObjectivesAlthough extensive national oral health data on dental caries and periodontal diseases in Japan are available, few studies have assessed the occlusal status of the Japanese population, and none are based on national survey data. The presence and prosthodontic conditions of the molar region are important for masticatory function, and the functional tooth unit (FTU) approach can be used to evaluate the occlusal status. Thus, using the national oral health survey data, this study investigated the occlusal status of the Japanese population using FTU.MethodsOverall, 3,605 adults (aged ≥20 years) who participated in the 2011 Japanese national oral health survey were included. FTUs were used as indices for evaluating the occlusal status. FTUs were calculated according to sex, age group, and the number of teeth present, and their associations were further analysed.ResultsThe number of teeth present, posterior teeth, and FTUs decreased with age in both men and women. In the age group of those ≥60 years, all only natural teeth-FTU (n-FTU) and natural teeth and artificial teeth from fixed prostheses or implant-supported FTU (nif-FTU) scores were <8. The total-FTU scores of all age groups, except the 60-69 and 70-79 years age groups, were >10.ConclusionThis is the first study to use FTUs and national oral health survey data to investigate the occlusal status in the Japanese population. People aged ≥60 years who have low n-FTU or natural teeth and artificial teeth from fixed prostheses or implant-supported FTU scores or those aged 60-70 years who have the lowest total-FTU scores require careful evaluation of masticatory performance.     

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma

Background:

Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients.

Methods:

Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC.

Results:

(1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT–PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145).

Conclusions:

Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.