The correlation of chondrule texture and magnesium isotope abundance in Allende meteorite

The Mg isotope abundance of the individual chondrules in the Allende meteorite was measured by ion microprobe mass analysis. The amounts of ^Mg excess with respect to the terrestrial fractionation line were obtained for each chondrule. Barred olivine and glassy chondrules tend to have relatively large ^Mg excess, whereas porphyritic and radial pyroxene chondrules have relatively small ^Mg excess. The following three factors were taken into consideration in connection with the formation process of these chondrules in the Allende meteorite; (1) the temperature conditions at the formation of the chondrules, (2) the relative abundance of each chondrule type, (3) the amount of ^Mg excess in each chondrule type. It is shown that chondrules formed at high temperature or by rapid cooling have relatively large ^Mg excess and their relative abundance is small, whereas chondrules formed at low temperature or by slow cooling tend to have small ^Mg excess and their relative abundance is large. A model of chondrule formation process in the early solar nebula is proposed to explain the relations between factors (1)-(3)

Vitamin K2 Has No Preventive Effect on Recurrence of Hepatocellular Carcinoma after Effective Treatment

Hepatocellular carcinoma (HCC) has a poor prognosis because of its high recurrence rate. Recently, vitamin K2 has been reported to inhibit the growth of HCC cell lines. To clarify the preventive effect of vitamin K2 on HCC recurrence, we studied 72 HCC patients who had been treated with surgical resection, local ablation or transarterial embolization: their etiologies were hepatitis B virus (n = 21), hepatitis C virus (n = 47), both B and C viruses (n = 2) and non-B or non-C virus (n = 2). We divided them into 2 groups: in one group, patients were treated with 45-mg/day vitamin K2 [K2-treated group (n = 23)], and in another, patients were not given vitamin K2 or a placebo [non-treated control group (n = 49)]. The obtained results between the 2 groups were compared. HCC recurred in 12 (52.2%) of the 23 K2-treated patients, and 22 (44.9%) of the 49 control patients. The differences in cumulative recurrence-free rate and cumulative survival rate between both groups were not significant (P = 0.92 and P = 0.08, respectively). As observed, chemopreventive effects of vitamin K2 at a clinically relevant dose on HCC recurrence were ineffective after effective treatment for HCC. Different regimens such as higher doses of vitamin K2 or combination therapy with other drugs may be worth testing to further explore the preventive effect on HCC recurrence

Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development

AbstractNotch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development

Cisplatin-induced programmed cell death ligand-2 expression is associated with metastasis ability in oral squamous cell carcinoma.

Programmed cell death ligands (PD-Ls) are expressed in tumor cells where they bind to programmed cell death-1, an immunocyte co-receptor, resulting in tumor cell evasion from the immune system. Chemotherapeutic drugs have been recently reported to induce the expression of PD-L, such as PD-L1, in some cancer cells. However, little is known regarding PD-L2 expression and its role in oral squamous cell carcinoma (OSCC). In this study, we examined the effect of cisplatin on the expression and regulation of PD-L2 in OSCC cell lines and analyzed malignant behavior in PD-L2-expressing cells using colony, transwell and transformation assays. In addition, we examined PD-L2 expression in the tumor tissues of OSCC patients using cytology and tissue microarray methods. In OSCC cell lines, cisplatin treatment upregulated PD-L2 expression, along with that of the drug efflux transporter ABCG2, via signal transducers and activator of transcription (STAT) 1/3 activation. Moreover, PD-L2-positive or PD-L2-overexpressing cells demonstrated upregulation in both invasion and transformation ability but not in proliferation compared with PD-L2-negative or PD-L2-silencing cells. PD-L2 expression was also observed in OSCC cells of cytology samples and tissue from OSCC patients. The intensity of PD-L2 expression was correlated with more malignant morphological features in the histological appearance and an invasive pattern. Our findings indicate that cisplatin-upregulated PD-L2 expression in OSCC via STAT1/3 activation and the expression of PD-L2 are likely to be associated with malignancy in OSCC. The PD-L2 expression in cisplatin-resistant OSCC cells may be a critical factor in prognosis of advanced OSCC patients.福岡歯科大学2019年

Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media

Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. Background: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. Methods: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF−/−) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. Results: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF−/− mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF−/− mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. Conclusion: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media

A practical synthesis of enantiopure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine by asymmetric reductive amination and the Curtius rearrangement

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部Enantiomerically pure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine was synthesized by the asymmetric reduction of a β-enamino ester formed from benzyl 2-oxocyclohexanecarboxylate and (R)-phenylethylamine, followed by hydrogenolysis, phthaloylation, and the Curtius rearrangement. © 2007

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease

[Background] Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferatoractivated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. [Methods] We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27?81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. [Results] After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. [Conclusion] Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD