Mesenchymal stem cells seeded onto nanofiber scaffold for myocardial regeneration.

Cardiac disease is the leading cause of mortality and disability worldwide. We investigated the role of undifferentiated adipose tissue-derived mesenchymal stem cells (ADMSC) alone and ADMSC seeded onto the electro-spun nanofibers (NF) for reconstructing damaged cardiac tissue in isoprenaline-induced myocardial infarction (MI) in rats. ADMSC were sorted by morphological appearance and by detection of cluster of differentiation (CD) surface antigens.

Osteoblast-Based Therapy-A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting.

Background: Osteoporosis is a metabolic bone disease characterized by low bone density resulting in increased fracture susceptibility. This research was constructed to uncover the potential therapeutic application of osteoblasts transplantation, generated upon culturing male rat bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteogenic medium (OM), OM containing gold (Au-NPs) or gold/hydroxyapatite (Au/HA-NPs) nanoparticles, in ovariectomized rats to counteract osteoporosis.

Methods: Forty rats were randomized into: (1) negative control, (2) osteoporotic rats, whereas groups (3), (4) and (5) constituted osteoporotic rats treated with osteoblasts yielded from culturing BM-MSCs in OM, OM plus Au-NPs or Au/HA-NPs, respectively.

Assessment of the prognostic value of methylation status and expression levels of FHIT, GSTP1 and p16 in non-small cell lung cancer in Egyptian patients.

Background: Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC).

NFkB inhibitors: strategies from poxviruses.

The orchestration of the inflammatory responses to both infection and tissue damage is arguably the key physiological function of NF-kappaB, and thus interference with the activation of NF-kappaB represents an exceptional strategy for a successful pathogen to exploit to counter multiple host innate defense processes through the targeting of a single host regulatory pathway. Because of their large genomes, which typically encode approximately 200 proteins, and their unusual independence from the host nuclear transcriptional machinery, poxviruses are especially well suited to manipulate the cytoplasmic activation of NF-kappaB. Indeed, poxviruses are known to encode multiple proteins that regulate the activation of NF-kappaB in a variety of different ways and these can be considered potential paradigms for the development of novel anti-inflammatory therapies and more effective vaccines.

Effect of UTP sugar and base modifications on vaccinia virus early gene transcription.

Prior efforts demonstrated that RNA oligonucleotides containing the transcription termination signal UUUUUNU stimulate premature termination of vaccinia virus early gene transcription, in vitro. This observation suggests that viral transcription termination may be an attractive target for the development of anti-poxvirus agents. Since short RNA molecules are readily susceptible to nuclease digestion, their use would require stabilizing modifications.

UUUUUNU oligonucleotide inhibition of RNA synthesis in vaccinia virus cores.

Recent results from this laboratory demonstrated the ability of U5NU-containing oligonucleotides to stimulate premature termination of early gene transcription in vitro. Further studies on the oligonucleotide sequence and structural requirements for stimulating premature termination demonstrated that only oligonucleotides possessing ribouracil U9 with a phosphodiester linkage are active. Because an oligonucleotide as short as 9 bases serves as an effective stimulator of premature transcription termination, we reasoned that short U5NU-containing oligonucleotides might serve as efficacious anti-poxvirus agents because they would prevent the synthesis of full-sized early mRNA.

UUUUUNU stimulation of vaccinia virus early gene transcription termination. Oligonucleotide sequence and structural requirements for stimulation of premature termination in vitro.

Vaccinia virus early genes are unique in that transcription terminates in a signal- and factor-dependent manner. Recent results from this laboratory demonstrated that a 22-mer RNA oligonucleotide containing a central U9 sequence exhibited sequence- and concentration-dependent stimulation of premature transcription termination and transcript release in trans. In an effort to better understand the different aspects of the U5NU stimulation of premature termination, we evaluated the activity of various oligonucleotides in vitro.

Effect of selected mutations in the C-terminal region of the vaccinia virus nucleoside triphosphate phosphohydrolase I on binding to the H4L subunit of the viral RNA polymerase and early gene transcription termination in vitro.

Vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH I) is an essential early gene transcription termination factor. The C-terminal end of NPH I binds to the N-terminal end of the H4L subunit (RAP94) of the virion RNA polymerase. This interaction is required for transcription termination and transcript release.

UUUUUNU oligonucleotide stimulation of vaccinia virus early gene transcription termination, in trans.

Vaccinia virus early gene transcription termination requires the vaccinia termination factor (VTF), NPH I, a single stranded DNA-dependent ATPase, the virion form of RNA polymerase containing the Rap 94 subunit, and the signal UUUUUNU, which resides in the nascent mRNA, located 30 to 50 bases upstream from the poly(A) addition site. Evidence indicates that a required termination factor acts through binding to the UUUUUNU signal. To further investigate the function of UUUUUNU, the ability of UUUUUNU containing oligonucleotides to inhibit transcription termination was tested.