Effects of a Chemically Synthesized Leucine-Rich Amelogenin Peptide (csLRAP) on Chondrogenic and Osteogenic Cells

福岡歯科大学2017年

Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia

<p>Abstract</p> <p>Background</p> <p>Ezetimibe (Zetia^®) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins.</p> <p>Results</p> <p>To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia.</p> <p>Conclusion</p> <p>In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.</p

Epidermal growth factor receptor mutation in combination with expression of MIG6 alters gefitinib sensitivity

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) signaling plays an important role in the regulation of cell proliferation, survival, metastasis, and invasion in various tumors. Earlier studies showed that the EGFR is frequently overexpressed in non-small-cell lung cancer (NSCLC) and EGFR mutations at specific amino acid residues in the kinase domain induce altered responsiveness to gefitinib, a small molecule EGFR tyrosine kinase inhibitor. However, the mechanism underlying the drug response modulated by EGFR mutation is still largely unknown. To elucidate drug response in EGFR signal transduction pathway in which complex dynamics of multiple molecules involved, a systematic approach is necessary. In this paper, we performed experimental and computational analyses to clarify the underlying mechanism of EGFR signaling and cell-specific gefitinib responsiveness in three H1299-derived NSCLC cell lines; H1299 wild type (H1299WT), H1299 with an overexpressed wild type EGFR (H1299EGFR-WT), and H1299 with an overexpressed mutant EGFR L858R (H1299L858R; gefitinib sensitive mutant).</p> <p>Results</p> <p>We predicted and experimentally verified that Mig6, which is a known negative regulator of EGFR and specifically expressed in H1299L858R cells, synergized with gefitinib to suppress cellular growth. Computational analyses indicated that this inhibitory effect is amplified at the phosphorylation/dephosphorylation steps of MEK and ERK.</p> <p>Conclusions</p> <p>Thus, we showed that L858R receptor mutation in combination with expression of its negative regulator, Mig6, alters signaling outcomes and results in variable drug sensitivity.</p

Ligand-Specific c-Fos Expression Emerges from the Spatiotemporal Control of ErbB Network Dynamics

SummaryActivation of ErbB receptors by epidermal growth factor (EGF) or heregulin (HRG) determines distinct cell-fate decisions, although signals propagate through shared pathways. Using mathematical modeling and experimental approaches, we unravel how HRG and EGF generate distinct, all-or-none responses of the phosphorylated transcription factor c-Fos. In the cytosol, EGF induces transient and HRG induces sustained ERK activation. In the nucleus, however, ERK activity and c-fos mRNA expression are transient for both ligands. Knockdown of dual-specificity phosphatases extends HRG-stimulated nuclear ERK activation, but not c-fos mRNA expression, implying the existence of a HRG-induced repressor of c-fos transcription. Further experiments confirmed that this repressor is mainly induced by HRG, but not EGF, and requires new protein synthesis. We show how a spatially distributed, signaling-transcription cascade robustly discriminates between transient and sustained ERK activities at the c-Fos system level. The proposed control mechanisms are general and operate in different cell types, stimulated by various ligands

ジユウ キジュツ カラ ミタ シンタイ ショウガイ ノ アル シセツ リヨウシャ ノ シュカンテキ ニーズ コベツ ノ ニーズ オヨビ ニーズ ノ ハイケイ ヨウイン

本研究は、「身体障害のある施設利用者の生活ニーズ」を把握するために実施した質問紙調査(先行研究)における「自由記述回答」を分析し、統計的データのみでは把握することのできない個別的なニーズや、主観的ニーズの背景要因について把握することを目的とした。 自由記述を45 サブグループ別に整理した結果、ニーズは一人ひとり個別性があるとともに、施設利用者のニーズは共通性もあることが示唆された。7 領域別に自由記述を分析し、以下の結論を得た。(1)主観的ニーズは、本人要因及び本人以外の要因により発生するとともに、同要因の影響を受けて判断・表出されることが示唆された。(2)本人以外及び本人と環境との相互作用を含む要因は、a)他利用者との関係性や、職員の支援体制及び職員との関係性を含む人的環境、b)施設の物理的環境や物理的な面での構造的問題、c)施設の方針や規則、支援体制などの施設内における内的体制、d)施設の地域環境や地域資源、e)福祉制度である。(3)自由記述に記された要望・意見は、支援の方向性を検討する上で示唆深い

Neutrophil elastase in amniotic fluid as a predictor of preterm birth after emergent cervical cerclage

Introduction. The aim of this study was to investigate neutrophil elastase (NE) in amniotic fluid as a potential marker for predicting pregnancy continuation. Material and methods. We enrolled 34 pregnant women with bulging fetal membrane during the second trimester who underwent emergent cerclage after confirming the absence of intrauterine infection (amniotic fluid glucose >= 15 mg/dL). Amniotic fluid NE levels were compared between women who completed and did not complete 30, 34, and 36 weeks of gestation, and the optimal cut-off value for predicting pregnancy continuation was estimated. Moreover, the differences in the duration of continued pregnancy were compared between women with NE levels above and below the optimal cut-off value. Results. The optimal cut-off value for NE in amniotic fluid that predicted pregnancy continuation beyond 30, 34, and 36 weeks of gestation was 180 ng/mL; this cut-off value had a sensitivity, specificity, positive predictive value, and negative predictive value of 84.0, 77.8, 91.3, and 63.7% beyond 30 weeks of gestation; 87.5, 80.0, 91.5, and 72.3% beyond 34 weeks of gestation; and 85.0, 71.4, 80.9, and 76.9% beyond 36 weeks of gestation, respectively. The duration of continued pregnancy from emergent cerclage to delivery was significantly longer in women with amniotic fluid NE = 180 ng/mL (44.8 +/- 14.3 days). Conclusion. The NE levels in amniotic fluid may serve as a useful marker for predicting the duration of continued pregnancy after cervical cerclage

Influenza A (H5N1) Viruses from Pigs, Indonesia

TOC summary: Pigs may serve as intermediate hosts in which this avian virus can adapt to mammals

Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line

Background: Exosomes play a major role in cell-to-cell communication, targeting cells to transfer exosomal molecules including proteins, mRNAs, and microRNAs (miRNAs) by an endocytosis-like pathway. miRNAs are small noncoding RNA molecules on average 22 nucleotides in length that regulate numerous biological processes including cancer pathogenesis and mediate gene downregulation by targeting mRNAs to induce RNA degradation and/or interfering with translation. Recent reports imply that miRNAs can be stably detected in circulating plasma and serum since miRNAs are packaged by exosomes to be protected from RNA degradation. Thus, profiling exosomal miRNAs are in need to clarify intercellular signaling and discover a novel disease marker as well. Methodology/Principal Findings: Exosomes were isolated from cultured cancer cell lines and their quality was validated by analyses of transmission electron microscopy and western blotting. One of the cell lines tested, a metastatic gastric cancer cell line, AZ-P7a, showed the highest RNA yield in the released exosomes and distinctive shape in morphology. In addition, RNAs were isolated from cells and culture media, and profiles of these three miRNA fractions were obtained using microarray analysis. By comparing signal intensities of microarray data and the following validation using RT-PCR analysis, we found that let-7 miRNA family was abundant in both the intracellular and extracellular fractions from AZ-P7a cells, while low metastatic AZ-521, the parental cell line of AZ-P7a, as well as other cancer cell lines showed no such propensity. Conclusions/Significance: The enrichment of let-7 miRNA family in the extracellular fractions, particularly, in the exosome

上顎洞および食道原発の二重癌の1剖検例

In cases of multiple primary cancers, the combination of head/neck cancer and upper digestive tract cancer is often found. However, it is extremely rare for maxillary sinus cancer and esophageal cancer to occur simultaneously. This paper reports on an autopsy case of double primary cancers of the maxillary sinus and esophagus. The patient had been suffering from carcinoma of the maxillary sinus for about 12 months but the lesion was uncontrollable. At autopsy, the following two primary carcinomas were found : one was a moderately differentiated squamous cell carcinoma originated from the maxillary sinus infiltrating into the hard palate and tongue, with metastases in several regional lymph nodes, a para-aortic lymph node and bilateral lungs. The other was a progressive, well-differentiated squamous cell carcinoma originated from the esophagus transformed mucosa with epithelial dysplasia. Furthermore, two masses of gastrointestinal mesenchymal tumors (GIMT) of the stomach were noted