Publication Title: 
The EMBO journal

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.

Gire, VÈronique
Roux, Pierre
Wynford-Thomas, David
Brondello, Jean-Marc
Dulic, Vjekoslav
Publication Title: 
FEBS letters

We recently demonstrated that 2,3,4,5,6-pentahydroxyxanthone (X5) inhibits the in vitro growth of both chloroquine-sensitive and multidrug-resistant strains of P. falciparum. To study the molecular basis of its antimalarial action, we tested X5 and selected hydroxyxanthone analogs as inhibitors of in vitro heme polymerization in a low ionic strength phosphate solution at mildly acidic pH. We found that addition of 1 Eq. of X5 resulted in complete inhibition of polymerization in this system whereas addition of up to 40 Eqs.

Ignatushchenko, M. V.
Winter, R. W.
Bächinger, H. P.
Hinrichs, D. J.
Riscoe, M. K.
Publication Title: 
The EMBO journal

The P-glycoprotein homolog of the human malaria parasite Plasmodium falciparum (Pgh-1) has been implicated in decreased susceptibility to several antimalarial drugs, including quinine, mefloquine and artemisinin. Pgh-1 mainly resides within the parasite's food vacuolar membrane. Here, we describe a surrogate assay for Pgh-1 function based on the subcellular distribution of Fluo-4 acetoxymethylester and its free fluorochrome. We identified two distinct Fluo-4 staining phenotypes: preferential staining of the food vacuole versus a more diffuse staining of the entire parasite.

Rohrbach, Petra
Sanchez, Cecilia P.
Hayton, Karen
Friedrich, Oliver
Patel, Jigar
Sidhu, Amar Bir Singh
Ferdig, Michael T.
Fidock, David A.
Lanzer, Michael
Publication Title: 
Molecular and Biochemical Parasitology

Efforts to move from malaria control to eradication will require new approaches to block malaria transmission, such as the development of anti-malarial drugs with gametocytocidal activity. Here fluorescent oxidoreduction indicator alamarBlue is used to develop a screen for gametocyte viability. The fluorescent signal increases linearly with gametocyte number (R(2)=0.99) and determination of the IC(50) of epoxomicin demonstrated the assay was reproducible and sensitive (IC(50) 2.16±0.57 nM, Z'-factor 0.81±0.01).

Tanaka, Takeshi Q.
Williamson, Kim C.
Publication Title: 
European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences

Traditionally Boswellia serrata extract is used in the Indian Ayurvedic medicine for the treatment of inflammatory diseases. In 2002 the EMEA designated Boswellia an orphan drug status for the treatment of peritumoral oedema. Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA). In continuation of the tests investigating the factors limiting bioavailability of boswellic acids, the present study examined the permeability of KBA and AKBA in human Caco-2 cell lines.

Krüger, Phillip
Kanzer, Johanna
Hummel, Jessica
Fricker, Gert
Schubert-Zsilavecz, Manfred
Abdel-Tawab, Mona
Publication Title: 
Phytotherapy research: PTR

Following chemotaxonomic evidence, the PE and CHCl(3) extracts of the roots of the botanical Angelica sinensis (Oliv.) Diels (Dang Gui) were investigated for in vitro anti-TB activity, in parallel to studying their serotonergic and GABAergic potential. The activities were confirmed to overlap chemically with the neurotropic active principles present in medium lipophilic fractions.

Deng, Shixin
Wang, Yuehong
Inui, Taichi
Chen, Shao-Nong
Farnsworth, Norman R.
Cho, Sanghyun
Franzblau, Scott G.
Pauli, Guido F.
Publication Title: 
ASN neuro

Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-D-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated.

He, Yan
Cui, Jiankun
Lee, James C.-M.
Ding, Shinghua
Chalimoniuk, Malgorzata
Simonyi, Agnes
Sun, Albert Y.
Gu, Zezong
Weisman, Gary A.
Wood, W. Gibson
Sun, Grace Y.
Publication Title: 
Memórias Do Instituto Oswaldo Cruz

The bioassay-guided fractionation of stems from Kielmeyera variabilis, traditionally used in Brazilian folk medicine, yielded assiguxanthone-B (1), kielcorin (4), 2,5-dihydroxybenzoic acid (3), and a mixture of xanthones containing assiguxanthone-B (1) and 1,3,5,6-tetrahydroxy-2-prenylxanthone (2) (1:1 w/w). The xanthone mixture inhibited Staphylococcus aureus and Bacillus subtilis at a concentration of 6.25 g/ml. When tested alone, the minimal inhibitory concentration of assiguxanthone-B was 25 g/ml against B. subtilis.

Pinheiro, Lucimar
Nakamura, Celso Vataru
Dias Filho, Benedito Prado
Ferreira, Antonio Gilberto
Young, Maria Claudia Marx
Cortez, Diógenes Aparicio Garcia
Publication Title: 
Journal of Chromatographic Science

In this study, metabolite profiling of Radix Saposhnikoviae from different geographical locations was performed using high-performance liquid chromatography-electrospray ionization time-of-flight mass spectrometry (HPLC-ESI-TOFMS) and multivariate statistical analysis technique. Principle component analysis (PCA) of the data shows that these samples could be roughly separated into three groups: Guan Fangfeng, Kou Fangfeng and Chuan Fangfeng. The potential chemical markers were discovered through the loading plot of PCA.

Li, Yue-Yue
Wang, Xin-Xia
Zhao, Liang
Zhang, Hai
Lv, Lei
Zhou, Gui-chen
Chai, Yi-Feng
Zhang, Guo-Qing
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