Cancer/Testis OIP5 and TAF7L Genes are Up-Regulated in Breast Cancer

Mobasheri, Maryam Beigom,Shirkoohi, Reza,Modarressi, Mohammad Hossein Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Breast cancer still remains as the most frequent cancer with second mortality rate in women worldwide. There are no validated biomarkers for detection of the disease in early stages with effective power in diagnosis and therapeutic approaches. Cancer/testis antigens are recently promising tumor antigens and suitable candidates for targeted therapies and generating cancer vaccines. We conducted the present study to analyze transcript changes of two cancer/testis antigens, OIP5 and TAF7L, in breast tumors and cell lines in comparison with normal breast tissues by quantitative real time RT-PCR for the first time. Significant over-expression of OIP5 was observed in breast tumors and three out of six cell lines including MDA-MB-468, T47D and SKBR3. Not significant expression of TAF7L was evident in breast tumors but significant increase was noted in three out of six cell lines including MDA-MB-231, BT474 and T47D. OIP5 has ssignificant role in chromatin organization and cell cycle control during cell cycle exit and normal chromosome segregation during mitosis and TAF7L is a component of the transcription factor IID, which is involved in transcription initiation of most protein coding genes. TAF7Lis located at X chromosome and belongs to the CT-X gene family of cancer/testis antigens which contains about 50% of CT antigens, including those which have been used in cancer immunotherapy.

Cd-doped SnO2-reduced Graphene Oxide Composite Nanofibrous Mats as CO Gas Sensors

Abbas Mobasheri,Saeed Parhoodeh,Gholamabbas Shams 한국섬유공학회 2022 Fibers and polymers Vol.23 No.3

In this study, SnO2 nanofibers and their modifications (Cd doping and making a composite with reduced grapheneoxide) were synthesized via electrospinning and employed as CO gas sensing. The enhanced sensing properties of Cd-dopedSnO2-RGO nanofibrous mat comparing to other counterparts could be ascribed to p-type behavior of RGO inside thenanofibers and catalytic activity and adding new sites for oxidation of cadmium elements, which offered flexible andoptimum gas sensing. These mats had a specific surface area of 74.56 m2/g with 10.65 nm cylindrical slender channels andaverage fiber diameter of 200.57 nm.

LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes

Elayyan, Jinan,Lee, Eun-Jin,Gabay, Odile,Smith, Christopher A.,Qiq, Omar,Reich, Eli,Mobasheri, Ali,Henrotin, Yves,Kimber, Susan J.,Dvir-Ginzberg, Mona The Federation of American Societies for Experimen 2017 The FASEB Journal Vol.31 No.7

<P>Reduced SIRT1 activity and levels during osteoarthritis (OA) promote gradual loss of cartilage. Loss of cartilage matrix is accompanied by an increase in matrix metalloproteinase (MMP) 13, partially because of enhanced LEF1 transcriptional activity. In this study, we assessed the role of SIRT1 in LEF1-mediated MMP13 gene expression in human OA chondrocytes. Results showed that MMP13 protein levels and enzymatic activity decreased significantly during SIRT1 overexpression or activation by resveratrol. Conversely, MMP13 gene expression was reduced in chondrocytes transfected with SIRT1 siRNA or treated with nicotinamide (NAM), a sirtuin inhibitor. Chondrocytes challenged with IL-113, a cytokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in increased MMP13 gene expression; however, overexpression of SIRT1 during IL-113 challenge impeded LEF1 levels and MMP13 gene expression. Previous reports showed that LEF1 binds to the MMP13 promoter and transactivates its expression, but we observed that SIRT1 repressed LEF1 protein and mRNA expression, ultimately reducing LEF1 transcriptional activity, as judged by luciferase assay. Finally, mouse articular cartilage from Sirt1-/presented increased LEF1 and MMP13 protein levels, similar to human OA cartilage. Thus, demonstrating for the first time that SIRT1 represses MMP13 in human OA chondrocytes, which appears to be mediated, at least in part, through repression of the transcription factor LEF1, a known modulator of MMP13 gene expression. Elayyan, J., Lee, E.-J., Gabay, O., Smith, C. A., Qiq, O., Reich, E., Mobasheri, A., Henrotin, Y., Kimber, S. J., Dvir-Ginzberg, M. LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes.</P>

Estimating the Myocardium’s Angle of Three-Dimensional Trajectory, Using the Tracking of Sequential Two-Dimensional Echocardiography Images

Manijhe Mokhtari-Dizaji,Mosayyeb Mobasheri,Faride Roshanali 한국심초음파학회 2014 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.22 No.1

Background: In this study, the angle of the myocardium’s trajectory in three dimensions (Ф) was estimated by simultaneoususe of long-axis and short-axis views of left ventricle septum two-dimensional images. Then correlation of three-dimensionaltrajectory’s angle with the rotation angle from the long (χ) and short (θ) axis views was estimated and compared at the three levelsof base, mid and apex of the interventricular septum wall. Methods: Two-dimensional echocardiography images of long- and short-axis views of 19 healthy men were recorded andanalyzed. Using an electrocardiogram of each individual, the images of the two views were synchronized. The interventricularseptum wall motion at the three levels of base, mid and apex were estimated, using a block matching algorithm throughoutthree cardiac cycles. Considering the defined system of coordinates and the position vectors in long and short-axis views, the3-dimensional angle of the trajectory was calculated. Results: Maxima of the Ф, θ, and χ angles were extracted at 16.33 ± 3.01, 10.61 ± 3.38, and 15.11 ± 3.30 degrees at base level,22.77 ± 4.95, 7.78 ± 2.96, and 16.72 ± 2.66 degrees at mid level and 14.60 ± 5.81, 10.37 ± 5.48, and 8.79 ± 3.32 degrees at apexlevel, respectively, of the septum wall, respectively. This study shows significant correlation between the angle of 3-dimensionaltrajectory (Ф) with the angle in short axis view (θ) of the septum wall at the apex level; and also with the angle in long axis view(χ) of the septum wall at base and mid levels. Conclusion: Due to the motion of the wall of the left ventricle in three dimensions, and the non-isotropic structure ofmyofibers, the angle of 3-dimensional trajectory was estimated using the speckle tracking method of 2-dimentionalechocardiography images.

Lactobacillus acidophilus and Lactobacillus crispatus Culture Supernatants Downregulate Expression of Cancer-testis Genes in the MDA-MB-231 Cell Line

Azam, Rosa,Ghafouri-Fard, Soudeh,Tabrizi, Mina,Modarressi, Mohammad-Hossein,Ebrahimzadeh-Vesal, Reza,Daneshvar, Maryam,Mobasheri, Maryam Beigom,Motevaseli, Elahe Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Lactobacilli are probiotics shown to have antitumor activities. In addition, they can regulate gene expression through epigenetic mechanisms. In this study, we aimed to assess anti tumor activities of Lactobacillus acidophilus and Lactobacillus crispatus on the MDA-MB-231 breast cancer cell line. The effects of culture supernatants were determined by MTT [3-(4,5-dimethylthiazol-2-y-2,5-diphenyltetrazolium bromide] assay. Changes in expression of 5 cancer-testis antigens (CTAs), namely AKAP4, ODF4, PIWIL2, RHOXF2 and TSGA10, were analyzed by quantitative real time RT-PCR. The culture supernatants of the 2 lactobacilli inhibited MDA-MB-231 cell proliferation. In addition, transcriptional activity of all mentioned CTAs except AKAP4 was significantly decreased after 24 hour treatment with culture supernatants. This study shows that Lactobacillus acidophilus and Lactobacillus crispatus have antiproliferative activity against MDA-MB-231 cells. In addition, these lactobacilli could decrease transcriptional activity of 4 CTAs. Previous studies have shown that expression of CTAs is epigenetically regulated, so it is possible that lactobacilli cause this expression downregulation through epigenetic mechanisms. As expression of CTAs in cancers is usually associated with higher grades and poor prognosis, downregulation of their expression by lactobacilli may have clinical implications.

Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram‐negative bacterial outer membrane

Park, Jeong Soon,Lee, Woo Cheol,Yeo, Kwon Joo,Ryu, Kyoung‐,Seok,Kumarasiri, Malika,Hesek, Dusan,Lee, Mijoon,Mobashery, Shahriar,Song, Jung Hyun,Kim, Seung Il,Lee, Je Chul,Cheong, Chaejoon,Jeon, Federation of American Society for Experimental Bi 2012 The FASEB Journal Vol.26 No.1

<P>The outer membrane protein A (OmpA) plays important roles in anchoring of the outer membrane to the bacterial cell wall. The C-terminal periplasmic domain of OmpA (OmpA-like domain) associates with the peptidoglycan (PGN) layer noncovalently. However, there is a paucity of information on the structural aspects of the mechanism of PGN recognition by OmpA-like domains. To elucidate this molecular recognition process, we solved the high-resolution crystal structure of an OmpA-like domain from Acinetobacter baumannii bound to diaminopimelate (DAP), a unique bacterial amino acid from the PGN. The structure clearly illustrates that two absolutely conserved Asp271 and Arg286 residues are the key to the binding to DAP of PGN. Identification of DAP as the central anchoring site of PGN to OmpA is further supported by isothermal titration calorimetry and a pulldown assay with PGN. An NMR-based computational model for complexation between the PGN and OmpA emerged, and this model is validated by determining the crystal structure in complex with a synthetic PGN fragment. These structural data provide a detailed glimpse of how the anchoring of OmpA to the cell wall of gram-negative bacteria takes place in a DAP-dependent manner.</P>

The Cell Shape-determining Csd6 Protein from <i>Helicobacter pylori</i> Constitutes a New Family of <small>L,D</small> -Carboxypeptidase

Kim, Hyoun Sook,Im, Ha Na,An, Doo Ri,Yoon, Ji Young,Jang, Jun Young,Mobashery, Shahriar,Hesek, Dusan,Lee, Mijoon,Yoo, Jakyung,Cui, Minghua,Choi, Sun,Kim, Cheolhee,Lee, Nam Ki,Kim, Soon-Jong,Kim, Jin Y American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.41

<▼1><P><B>Background:</B> Csd6 is one of the cell shape-determining proteins in <I>H. pylori</I>.</P><P><B>Results:</B> The active site of Csd6 is tailored to function as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase in the peptidoglycan-trimming process.</P><P><B>Conclusion:</B> Csd6 constitutes a new family of <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase.</P><P><B>Significance:</B> The substrate limitation of Csd6 is a strategy that <I>H. pylori</I> uses to regulate its helical cell shape and motility.</P></▼1><▼2><P><I>Helicobacter pylori</I> causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In <I>H. pylori</I>, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases. Mass analyses confirm that Csd6 functions only as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase and not as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase. The <SMALL>D</SMALL>-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and <I>in silico</I> docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that <I>H. pylori</I> Csd6 and its homologs constitute a new family of <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of <I>H. pylori</I>.</P></▼2>