Effects of TNF-a on lysyl oxidase in Wnt induced cells at post-transcriptional level by miRNA

Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2013 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 50-67.Objective: Lysyl oxidase (LOX) dependent cross-linking is deficient in diabetic bone, contributing to osteopenia. Here we Investigate regulation of lysyl oxidase by Wnt3a and TNF-a in a mesenchymal stem cell line as a model for a novel mechanism of diabetic osteopenia. Methods: Wnt3a-treated C3Hl 0Tl/2 cells were treated with or without of TNF-a. Lysyl oxidase expression ( qPCR) and mRNA stability were measured. A comprehensive PCR-based microarray screen (Qiagen/SA Biosciences) was next performed to_ identify miRNAs which regulate LOX mRNA stability in response to TNF-a. The functionality of identified miRNA was independently determined by the use of miRNA mimics. Results: Wnt3a up-regulated LOX up to 3.2-fold by treating C3H10Tl/2 cells with Wnt3a compared to controls. TNF-a (20 ng/ml) blocked Wnt3a up-regulation of LOX. TNF-a decreased the stability of LOX mRNA determined in the presence of a transcription inhibitor in control- and Wnt3a plus TNF-a-treated cells. A micro (miR) array screen performed on RNA isolated from Wnt3a plus TNF-a treated and control cells identified miR203 as being up-regulated 13-fold by TNF-a. Independent analyses ... [TRUNCATED

低比重リポ蛋白受容体関連蛋白のマクロファージによる12/15-リポキシゲナーゼを介したLDL酸化における必要性

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1602号, 学位授与年月日 : 平成15年6月30日, 学位授与大学 : 金沢大

STUDY ON ANTI-TUMOR EFFECT OF TOTAL GLYCOSIDES FROM RADIX PAEONIAE RUBRA IN S180 TUMOR-BEARING MICE

The objective of the paper was to study the anti-tumor effect of total glycosides from Radix paeoniae rubra in S180 tumor-bearing mice, and to preliminarily explore its mechanism of action. Mice were made into S180 solid tumor model, grouped and administered with the extracts; tumor inhibition rate was measured by harvesting the tumors, and serum IL-2 and IL-4 levels were measured by taking blood samples. Total glycosides of Radix paeoniae rubra significantly inhibited the growth of tumor cells in tumor-bearing organisms, enhanced the cytotoxic activity of NK cells, and increased the serum IL-2 and IL-4 levels. Total glycosides of Radix paeoniae rubra have some anti-tumor effect in vivo, which might have been accomplished through the regulation of the immune system

Scintillation efficiency measurement of Na recoils in NaI(Tl) below the DAMA/LIBRA energy threshold

The dark matter interpretation of the DAMA modulation signal depends on the NaI(Tl) scintillation efficiency of nuclear recoils. Previous measurements for Na recoils have large discrepancies, especially in the DAMA/LIBRA modulation energy region. We report a quenching effect measurement of Na recoils in NaI(Tl) from 3keV$_{\text{nr}}$ to 52keV$_{\text{nr}}$, covering the whole DAMA/LIBRA energy region for light WIMP interpretations. By using a low-energy, pulsed neutron beam, a double time-of-flight technique, and pulse-shape discrimination methods, we obtained the most accurate measurement of this kind for NaI(Tl) to date. The results differ significantly from the DAMA reported values at low energies, but fall between the other previous measurements. We present the implications of the new quenching results for the dark matter interpretation of the DAMA modulation signal

miR-499-5p Attenuates Mitochondrial Fission and Cell Apoptosis via p21 in Doxorubicin Cardiotoxicity

Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but its cardiotoxicity limits its clinical application. A better understanding of the molecular mechanisms underlying DOX cardiotoxicity will benefit clinical practice and remedy heart failure. Our present study observed that DOX caused cardiomyocyte (H9c2) apoptosis via the induction of abnormal mitochondrial fission. Notably, the expression levels of p21 increased in DOX-treated cardiomyocytes, and the silencing of p21 using siRNA greatly attenuated mitochondrial fission and apoptosis in cardiomyocytes. We also found that miR-499-5p could directly target p21 and attenuated DOX-induced mitochondrial fission and apoptosis. The role of the miR-499-5p-p21 axis in the prevention of DOX cardiotoxicity was also validated in the mice model. DOX treatment induced an upregulation of p21, which induced subsequent abnormal mitochondrial fission and myocardial apoptosis in mouse heart. Adenovirus-harboring miR-499-5p-overexpressing mice exhibited significantly reduced p21 expression, mitochondrial fission and myocardial apoptosis in hearts following DOX administration. The miR-499-5p-overexpressing mice also exhibited improved cardiomyocyte hypertrophy and cardiac function after DOX treatment. However, miR-499-5p was not involved in the DOX-induced apoptosis of cancer cells. Taken together, these findings reveal an emerging role of p21 in the regulation of mitochondrial fission program. miR-499-5p attenuated mitochondrial fission and DOX cardiotoxicity via the targeting of p21. These results provide new evidence for the miR-499-5p-p21 axis in the attenuation of DOX cardiotoxicity. The development of new therapeutic strategies based on the miR-499-5p-p21 axis is a promising path to overcome DOX cardiotoxicity as a chemotherapy for cancer treatment

Rapid Visual Detection of Pathogenic Streptococcus suis Type 2 through a Recombinase Polymerase Amplification Assay Coupled with Lateral Flow Test

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen causing serious disease and even death in pigs and humans. Public health events and economic losses caused by SS2 have prompted widespread concern. Because of the unavailability of vaccines, the development of rapid detection methods for timely diagnosis of SS2 infection or contaminated products, and monitoring of its prevalence in susceptible animals and populations, is required to aid in the prevention and control of SS2 infections. Several sets of primers and one probe for a recombinase polymerase amplification (RPA) assay targeting the cpsJ2 gene were designed and synthesized. Lateral flow (LF) tests in combination with RPA were used to provide visual results. Primers with high amplification efficiency were screened, and the reaction system was optimized. Indicators of detection effectiveness were evaluated. The established method had a detection limit of 100 copies/reaction for recognizing SS2 rather than other organisms. The sensitivity was 100%, as evaluated in infected animal samples. The detection could be completed within 20 min and required only constant temperature equipment. The established rapid, visual, sensitive and specific RPA-LF assay showed superior detection performance and is expected to be widely applied to fight SS2 infection in resource-limited areas

Patterns and mechanisms of coseismic and postseismic slips of the 2011 M W 7.1 Van (Turkey) earthquake revealed by multi-platform synthetic aperture radar interferometry

On 23rd October 2011, a MW 7.1 reverse slip earthquake occurred in the Bardakçı-Saray thrust fault zone in the Van region, Eastern Turkey. Earlier geodetic studies have found different slip distributions in terms of both magnitude and pattern. In this paper, we present several COSMO-SkyMED (CSK), Envisat ASAR and RADARSAT-2 interferograms spanning different time intervals, showing that significant postseismic signals can be observed in the first three days after the mainshock. Using observations that combine coseismic and postseismic signals is shown to significantly underestimate coseismic slip. We hence employed the CSK pair with the minimum postseismic signals to generate one conventional interferogram and one along-track interferogram for further coseismic modelling. Our best-fit coseismic slip model suggests that: (1) this event is associated with a buried NNW dipping fault with a preferable dip angle of 49° and a maximum slip of 6.5 m at a depth of 12 km; and (2) two unequal asperities can be observed, consistent with previous seismic solutions. Significant oblique aseismic slip with predominant left-lateral slip components above the coseismic rupture zone within the first 3 days after the mainshock is also revealed by a postseismic CSK interferogram, indicating that the greatest principal stress axis might have rotated due to a significant stress drop during the coseismic rupture

The promising role of miRNAs in radioresistance and chemoresistance of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that develops in the nasopharynx. It has a distinct ethnic and geographical distribution, and emerging evidence suggests that it is an ecological disease. Most patients respond well to radiation combined with chemotherapy as the primary treatment for NPC. However, some patients will eventually develop radio resistance and chemoresistance, resulting in recurrence and metastasis, which is a primary cause of poor prognosis. The processes underlying radio resistance and chemoresistance in NPC are complex and unknown. MicroRNAs (miRNAs) are endogenic non-coding RNA molecules. They play a role in a variety of cell functions as well as development of disease such as cancer. There has been considerable data demonstrating the existence of numerous aberrant miRNAs in cancer tissues, cells, and biofluids, which indicates the importance of studying the influence of miRNAs on NPC. Therefore, this review comprehensively analyzes the elaborate mechanisms of miRNAs affecting the radio resistance and chemoresistance of NPC. Multiple tumor-specific miRNAs can be employed as therapeutic and prognostic biological indicators