Castalagin and vescalagin purified from leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry: Dual inhibitory activity against PARP1 and DNA topoisomerase II.

Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) is one of the most promising strategies for cancer chemotherapy, and a number of inhibitors possessing nicotinamide-like structures are being developed. To discover new types of PARP1 inhibitors, we screened a large number of substances of plant origin and isolated two inhibitory substances from the leaves of Syzygium samarangense (Blume) Merrill & L.M.

15-Deoxy-Δ12,14-prostaglandin J2 induces PPARγ- and p53-independent apoptosis in rabbit synovial cells.

A ligand of peroxisome proliferator-activated receptor γ (PPARγ), 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) induces apoptosis in various cells. However, the mechanism appears to be complex and cell-type specific. We investigated the mechanism of 15d-PGJ2-induced apoptosis of rabbit synovial cells.

Capture of dengue virus type 3 using anionic polymer-coated magnetic beads.

Dengue virus (DENV) is a mosquito-borne virus and can be transmitted to humans by mosquito vectors. Although surveillance of dengue virus-infected mosquitoes is the most effective way of controlling DENV infections, detection of DENVs in mosquitoes is limited by the low sensitivity of available detection methods. We here report a method for capturing DENV type 3 (DENV-3) from mosquito cells using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate).

[Results of a post-marketing surveillance of meropenem for children].

The post-marketing surveillance of meropenem for children was conducted between May 2004 and September 2006. The safety and the efficacy were analyzed in 1210 cases and 1004 cases, respectively. The results of this surveillance were as follows: The incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 14.

Capture of infectious borna disease virus using anionic polymer-coated magnetic beads.

Borna disease virus (BDV) is a noncytolytic, neurotrophic virus that infects a range of vertebrates, including all warm-blooded animals and possibly humans. Although BDV infections are thought to cause neurological disorders, evidence of the presence of the virus in tissues or blood of psychiatric patients is limited, possibly due to the low sensitivity of detection methods. Here, a simple method for capturing BDV has been developed using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate).

Fundamentals of prions and their inactivation (review).

Prion is an infectious particle composed of an abnormal isoform of the prion protein (PrPSc) and causes prion diseases such as bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD) and scrapie. Host cells express cellular prion protein (PrPC), which plays roles in normal functions such as anti-oxidative stress. PrPSc is derived from PrPC and produced by conformational conversion.

Structure of the prion protein and its gene: an analysis using bioinformatics and computer simulation.

Prion protein (PrP) gene encodes cellular PrP (PrPC), a glycosylphosphatidylinositol (GPI)-anchored cell membrane protein indispensable for infections of prion, which causes Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. Although PrPC is known to be converted into an abnormal isoform (PrPSc) upon prion infection and play an important role in prion diseases, the mechanisms involved remain unclear, partly due to the insolubility of PrPSc, which prevents experimental biochemical and biophysical analyses. Recently, with improvements in computer power and methods, computer analyses have been contributing more to prion studies.

Mechanical stretch enhances NF-kappaB-dependent gene expression and poly(ADP-ribose) synthesis in synovial cells.

Temporomandibular joint disorders (TMD) show complex symptoms associated with inflammation, pain and degeneration of the peripheral tissues including synovium. Although it is believed that excessive mechanical stress on synovium causes development of TMD, the molecular mechanism by which mechanical stress triggers TMD has still remained unclear. In order to examine the effect of mechanical stress on synoviocytes, rabbit synovial cells were cyclically stretched in vitro.

15-Deoxy-Delta(12,14)-prostaglandin J(2) impairs the functions of histone acetyltransferases through their insolubilization in cells.

The cyclopentenonic prostaglandin 15-deoxy-Delta(12,14)-PG J(2) (15d-PGJ(2)) is a metabolite derived from PGD(2). Although 15d-PGJ(2) has been demonstrated to be a potent ligand for peroxisome proliferator activated receptor gamma (PPARgamma), the functions are not fully understood. In order to examine the effect of 15d-PGJ(2) on histone acetyltransferases (HATs), several lines of cell including mouse embryonic fibroblast (MEF) cells were exposed to 15d-PGJ(2).

Up-regulation of NFkappaB-responsive gene expression by DeltaNp73alpha in p53 null cells.

Transactivation domain (TAD)-truncated p73, DeltaNp73, associates with p53, resulting in suppression of p53's functions. Using p53 null cell lines, we examined whether or not DeltaNp73 can regulate gene expression in a p53-independent manner. When DeltaNp73alpha was co-transfected with a luciferase reporter plasmid with various enhancer elements, NFkappaB-responsive luciferase gene expression was selectively up-regulated by DeltaNp73alpha, but not by other p73-isoforms with TAD and DeltaNp73beta.

Poly(ADP-ribose)polymerase-1 is required for integration of the human immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and murine cells.

This study examined the efficiency of human immunodeficiency virus type 1 (HIV-1) integration in poly(ADP-ribose)polymerase-1 (PARP-1)-deficient murine cells and in human cell lines transfected with small interfering RNA against PARP-1 (PARP-1 siRNA). To semi-quantify the amount of integrated HIV-1 genome, real-time nested PCR was carried out using primers specific for Alu and alphoid DNA combined with primers for the HIV-1 genome. The results showed that the integration efficiency of the HIV-1 genome near Alu DNA, which is randomly distributed in the chromosome, is reduced in PARP-1-deficient murine cells, but not in PARP-1 siRNA-transfected human cells.

RNA interference directed against Poly(ADP-Ribose) polymerase 1 efficiently suppresses human immunodeficiency virus type 1 replication in human cells.

We established small interfering RNA (siRNA) directed against poly(ADP-ribose) polymerase 1 (PARP-1) that effectively reduces the expression of PARP-1 in two human cell lines. Established siRNA against PARP-1 significantly suppressed human immunodeficiency virus type 1 (HIV-1) replication, as well as the activation of the integrated HIV-1 long terminal repeat promoter. These results indicate that PARP-1 is required for efficient HIV-1 replication in human cells.

Regulation of HSF1-responsive gene expression by N-terminal truncated form of p73alpha.

DNp73 is a transactivation domain (TAD)-truncated form of p73. The ability of DNp73alpha to regulate gene expression was examined using reporter assays with luciferase gene constructs. Among various promoter-regulated reporter genes tested, heat shock factor (HSF)-responsive gene expression was selectively activated by DNp73alpha, but not by other p73-isoforms with TAD and DNp73beta.

Expression of histone acetyltransferases was down-regulated in poly(ADP-ribose) polymerase-1-deficient murine cells.

NF-kappaB-dependent, as well as human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR)-dependent, reporter gene expression was significantly impaired in cells derived from poly(ADP-ribose) polymerase-1 (PARP-1)-knockout (PARP-1 -/-) mice. In addition, the level of protein acetylation was markedly lower in PARP-1 -/- cells than control (PARP-1 +/+) cells. Surprisingly, the expression levels of histone acetyltransferases (HATs), p300, cAMP response element-binding protein-binding protein (CBP), and p300/CBP-associated factor (PCAF), were significantly reduced in PARP-1 -/- cells, as compared with PARP-1 +/+ cells.

Alteration of apoptotic protease-activating factor-1 (APAF-1)-dependent apoptotic pathway during development of rat brain and liver.

Brain and liver extracts of rats at different stages after birth were examined for cytochrome c/dATP-dependent caspase (DEVDase)-activation (mitochondria pathway) in vitro. The caspase-activating activity in the brain extracts rapidly decreased after birth, reaching approximately 50 and 5%, at 1 and 2 weeks, respectively, of that in a 3-days- newborn sample, and essentially no caspase-activation was detected in the adult rat brain extracts. Such a dramatic change was not detected in the liver samples, suggesting that the observed abrogation of the cytochrome c-dependent mitochondria pathway after birth is a brain-specific event.