Mineral trioxide aggregate induces osteoblastogenesis via Atf6

AbstractMineral trioxide aggregate (MTA) has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III) and matrix metalloproteinases (MMP-9 and MMP-13), suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin) but not Bmp2 (bone morphogenetic protein-2) mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER) stress response transcription factor) mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6) markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection

Effect of hospitalization on fetal growth

Objective : We aimed to demonstrate the effect of prolonged hospitalization on fetal growth in cases of threatened preterm labor (TPL). Methods : In this retrospective cohort study, we included women who received prenatal care for TPL but delivered their child after 36 weeks of gestation. These were compared with a control group of healthy pregnant women and fetuses delivered at term. Fetal growth was compared using biparietal diameter, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) assessed using ultrasonography at 18, 26, 30, and 36 weeks of gestation. Neonatal parameters at birth were also compared. Results : In total, we enrolled 228 control women and 114 women with TPL who were treated with hospitalization, including bed rest. The AC at 30 and 36 weeks of gestation and EFW at 36 weeks of gestation were smaller in women treated with bed rest than for normal pregnant women. The mean duration of pregnancy was shorter in the hospitalization group than in the control group. Neonatal weight, length, head circumference, and chest circumference at birth were smaller after prolonged hospitalization for TPL than after normal pregnancy. Conclusion : Prolonged hospitalization for threatened preterm labor is associated with impaired fetal growth, particularly AC

Rapid Disease Progression of Advanced Non-small Cell Lung Cancer Five Months after Cessation of Pembrolizumab

We report a case of late-onset hyperprogressive disease after cessation of a PD-1 inhibitor. A male was diagnosed with metastatic lung adenocarcinoma with little progression for 2 months before treatment. He received pembrolizumab as a second-line treatment and was subsequently prescribed docetaxel for 3 months until a slight increase in pleural effusion. At the time of progression to docetaxel, he commenced prednisolone because of immune-system-related diarrhea. After that, his general condition rapidly worsened with severe fatigue and hypoxia. Computed tomography revealed a massive increase of pleural effusion and replacement of almost the entire liver with cancer over a period of 5 weeks

Rotational spectroscopy of the thioformaldehyde isotopologues H2_2CS and H2_2C34^{34}S in four interacting excited vibrational states and an account on the rotational spectrum of thioketene, H2_2CCS

An investigation of the rotational spectrum of the interstellar molecule thioformaldehyde between 110 and 377 GHz through a pyrolysis reaction revealed a multitude of absorption lines assignable to H$_2$CS and H$_2$C$^{34}$S in their lowest four excited vibrational states besides lines of numerous thioformaldehyde isotopologues in their ground vibrational states reported earlier as well as lines pertaining to several by-products. Additional transitions of H$_2$CS in its lowest four excited vibrational states were recorded in selected regions between 571 and 1386 GHz. Slight to strong Coriolis interactions occur between all four vibrational states with the exception of the two highest lying states because both are totally symmetric vibrations. We present combined analyses of the ground and the four interacting states for our rotational data of H$_2$CS and H$_2$C$^{34}$S. The H$_2$CS data were supplemented with two sets of high-resultion IR data in two separate analyses. The $v_2 = 1$ state has been included in analyses of Coriolis interactions of low-lying fundamental states of H$_2$CS for the first time and this improved the quality of the fits substantially. We extended furthermore assignments in $J$ of transition frequencies of thioketene in its ground vibrational state.Comment: 23 pages including figures, tables, and references; Mol. Phys., accepted (for the Tim Lee memorial issue

Vitamin D during pregnancy in Japanese

We aimed to demonstrate that the serum 25-hydroxyvitamin D (25(OH)D) level in maternal and umbilical cord blood has a seasonal variation in Japanese women. The study cohort comprised 256 healthy Japanese women with a singleton pregnancy who delivered after 36 gestational weeks between 2012 and 2015. The season at delivery was categorized for 3 months and recorded as “spring”, “summer”, “autumn” and “winter”. Subjects were divided into four groups according to season. A sample of peripheral venous blood at 35-36 gestational weeks and blood from the umbilical vein at delivery were taken. The mean serum 25(OH)D concentration (ng/mL) in maternal blood for each season (spring, summer, autumn and winter) was 18.0 (±6.7), 17.1 (±5.1), 21.6 (±8.0) and 16.0 (±5.1), whereas that for umbilical cord blood was 8.8 (±3.6), 8.6 (±2.6), 10.7 (±3.5) and 8.6 (±2.1), respectively. The mean serum 25(OH)D concentration of maternal and umbilical cord blood in autumn was higher than that for the other three seasons. In pregnant Japanese women, the mean serum 25(OH)D concentration in maternal and umbilical cord blood was affected by the season of delivery, with both being highest in autumn. Regardless of the season, the maternal serum concentration of 25(OH)D was low in Japan

Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme

This research was originally published in the Journal of Biological Chemistry. T Yamada, M Matsushima, K Inaka, T Ohkubo, A Uyeda, T Maeda, K Titani, K Sekiguchi and M Kikuchi. Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme. J. Biol. Chem. 1993; 268: 10588-10592 © the American Society for Biochemistry and Molecular Biolog

Electrical cardiometry for hemodynamics

Few reports have focused on hemodynamics around delivery in pregnant women because of the difficulty of continuous and noninvasive measurement. Electrical cardiometry allows noninvasive continuous monitoring of hemodynamics and has recently been used in non-pregnant subjects. We compared the use of electrical cardiometry versus transthoracic echocardiography in healthy pregnant women and evaluated hemodynamics immediately after vaginal delivery. In Study 1, electrical cardiometry and transthoracic echocardiography were used to measure cardiac output in 20 pregnant women with threatened premature delivery. A significant correlation was found between the two methods, with electrical cardiometry showing the higher cardiac output. In Study 2, heart rate, stroke volume, and cardiac output were continuously measured in 15 women during vaginal delivery up to 2 h postpartum. Cardiac output increased markedly because of an increased heart rate and stroke volume at the time of newborn delivery. The heart rate then immediately returned to baseline, while cardiac output remained elevated for at least 2 h after delivery because of a sustained high stroke volume. Electrical cardiometry was as readily available as transthoracic echocardiography for evaluating hemodynamics and allowed for continuous measurement during labor. High intrapartum cardiac output was sustained for at least 2 h after vaginal delivery