Thonningiiflavanonol A and thonningiiflavanonol B, two novel flavonoids, and other constituents of Ficus thonningii Blume (Moraceae).

A phytochemical study of Ficus thonningii has led to the isolation of two previously unreported compounds, thonningiiflavanonol A and thonningiiflavanonol B together with 16 known compounds: shuterin, naringenin, syringic acid, p-hydroxybenzoic acid, genistein, 5,7,3',4',5'-pentahydroxyflavanone, luteolin, methylparaben, aromadendrin, garbanzol, dihydroquercetin, 5,7,3'-trihydroxyflavanone, ß-sitosterol, sitosterolglucoside, lupeol acetate, and taraxerol. Their structures were elucidated on the basis of spectroscopic data. The new compounds and extracts displayed potent antioxidant activity.

Dihydro-beta-agarofuran sesquiterpenes and pentacyclic triterpenoids from the root bark of Osyris lanceolata.

Three new dihydro-beta-agarofuran polyesters, 1alpha,9beta-difuranoyloxy-2-oxodihydro-beta-agarofuran (1), 1alpha,9beta-difuranoyloxy-2-oxo-3-enedihydro-beta-agarofuran (2), and 1alpha,9beta-difuranoyloxydihydro-beta-agarofuran (3), have been isolated from the CHCl(3) extract of the root bark of Osyris lanceolata, together with two known pentacylic triterpenoids, 4 and 5. Compounds 1-5 did not scavenge the DPPH radical within 30 min of reaction time. All five compounds displayed antifungal activity against Candida albicans. Compounds 1, 3, 4, and 5 showed antibacterial activity against the Gram-positive Bacillus subtilis and Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa, with 4 and 5 being the most active. Compound 2 displayed weak antibacterial activity only against Escherichia coli.

Intermittent granulocyte colony-stimulating factor for neutropenia management in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone.

Neutropenia is a major dose-limiting toxicity associated with lenalidomide in relapsed/refractory multiple myeloma (MM). The optimal dosing schedule of granulocyte colony-stimulating factor (G-CSF) is unclear. We developed an intermittent G-CSF schedule (4-6 doses per cycle) initiated upon onset of grade 3-4 neutropenia. Of 216 patients with relapsed/refractory MM treated at our center with lenalidomide/dexamethasone on an Expanded Access Program, there was a high incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was common (59%), and dose reductions were required in 40% of G-CSF recipients, most due to thrombocytopenia. G-CSF recipients had a longer duration on therapy and achieved a higher rate and depth of response. Intermittent G-CSF may be an effective approach for lenalidomide dose-preservation, which may lead to improved outcomes, although it does not prevent infections or thrombocytopenia-related dose limitations.

Radical scavenging activity and total phenolic content of extracts of the root bark of Osyris lanceolata.

The root bark of Osyris lanceolata was screened for its antioxidant potential using three variations of the DPPH radical scavenging method viz a TLC-autographic assay, a semi-quantitative TLC assay, and a spectrophotometric assay. The total phenolic content was evaluated as gallic acid equivalents (GAE) using the Folin-Ciocalteu method. The powdered root bark was extracted sequentially with n-hexane, chloroform, methanol and 90% methanol/water. A separate supercritical fluid extraction (SFE) of the root bark was also carried out. The radical scavenging ability, as measured by IC50 values, was found to be 48.4 +/- 0.4 and 49.5 +/- 1.9 microg/mL for the 90% methanol/water and methanol extracts respectively, while those of the chloroform, n-hexane, and SFE extracts were found to be > 250 microg/mL. Under the same conditions, the values for the standards, ascorbic acid and gallic acid, were found to be 38.70 +/- 0.08 and 2.86 +/- 0.01 microg/mL respectively. The radical scavenging power of the five extracts correlated positively with the total phenolic content and was ranked in the following decreasing order: 90% methanol/water > methanol > chloroform > SFE > n-hexane with total phenolic contents of 290.2 +/- 3.3, 271.0 +/- 3.7, 74.4 +/- 0.8, 62.5 +/- 0.4 and 49.5 +/- 1.9 mg GAE/g of dry extract, respectively. The 90% methanol/water and methanol extracts showed several components with high antioxidant activity displaying fast kinetics in both TLC assays, while the chloroform, SFE, and n-hexane extracts exhibited slow kinetics antioxidant activity.

Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase.

The destabilization of endothelial nitric-oxide synthase (eNOS) mRNA in hypoxic endothelial cells may be important in the etiology of vascular diseases, such as pulmonary hypertension. Recently, an overlapping antisense transcript to eNOS/NOS3 was implicated in the post-transcriptional regulation of eNOS. We demonstrate here that expression of sONE, also known as eNOS antisense (NOS3AS) or autophagy 9-like 2 (APG9L2), is robustly induced by hypoxia or functional deficiency of von Hippel-Lindau protein. sONE is also up-regulated in the aortas of hypoxic rats. In hypoxic endothelial cells, sONE expression negatively correlates with eNOS expression. Blocking the hypoxic induction of sONE by RNA interference attenuates the fall in both eNOS RNA and protein. We provide evidence that the induction of sONE primarily involves transcript stabilization rather than increased transcriptional activity and is von Hippel-Lindaubut not hypoxia-inducible factor 2alpha-dependent. We also demonstrate that sONE transcripts are enriched in the nucleus of normoxic cells and that hypoxia promotes an increase in the level of cytoplasmic and polyribosome-associated, sONE mRNA. The finding that eNOS expression can be regulated by an overlapping cis-antisense transcript in a stimulus-dependent fashion provides evidence that sense/antisense interactions may play a previously unappreciated role in vascular disease pathogenesis.