Impact of two different rodent diets on maternal ethanol consumption, serum ethanol concentration and pregnancy outcome measures.

Recent studies report varying levels of ethanol consumption by rodents maintained on different commercially available laboratory diets. As varied ethanol consumption by dams may impact offspring outcome measures in prenatal ethanol exposure paradigms, we compared ethanol consumption by rats maintained on the Envigo 2920 diet, used in our vivarium, with an isocalorically equivalent PicoLab 5L0D diet used in some alcohol consumption studies. Compared to 5L0D diet, female rats maintained on 2920 diet consumed 14% less ethanol during daily 4-h drinking sessions prior to pregnancy and 28% less ethanol during gestation. Rat dams consuming 5L0D diet gained significantly less weight during pregnancy. However, their pup birth weights were significantly higher. A subsequent study revealed that hourly ethanol consumption was not different between diets during the first 2 h, but was significantly lower on 2920 diet at the end of the third and fourth hours. The mean serum ethanol concentration in 5L0D dams after the first 2 h of drinking was 46 mg/dL compared to 25 mg/dL in 2920 dams. Further, ethanol consumption at the 2-h blood sampling time point was more variable in 2920 dams compared to 5L0D dams. An in vitro analysis mixing each powdered diet with 5% ethanol in acidified saline revealed that a 2920 diet suspension adsorbed more aqueous medium than the 5L0D diet suspension. The total ethanol remaining in aqueous supernatant of 5L0D mixtures was nearly twice the amount of ethanol in supernatants of the 2920 mixtures. These results suggest that the 2920 diet expands to a greater extent in aqueous medium than the 5L0D diet. We speculate that increasing adsorption of water and ethanol by the 2920 diet may reduce or delay the amount of ethanol absorbed and may decrease serum ethanol concentration to a greater extent than would be predicted from the amount of ethanol consumed.

Aurantoside C Targets and Induces Apoptosis in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is a subtype of breast cancers that currently lacks effective targeted therapy. In this study, we found that aurantoside C (C828), isolated from the marine sponge Manihinea lynbeazleyae collected from Western Australia, exhibited higher cytotoxic activities in TNBC cells compared with non-TNBC (luminal and normal-like) cells. The cytotoxic effect of C828 was associated to the accumulation of cell at S-phase, resulting in the decline of cyclin D1, cyclin E1, CDK4, and CDK6, and an increase in p21. We also found that C828 inhibited the phosphorylation of Akt/mTOR and NF-kB pathways and increased the phosphorylation of p38 MAPK and SAPK/JNK pathways, leading to apoptosis in TNBC cells. These effects of C828 were not observed in non-TNBC cells at the concentrations that were cytotoxic to TNBC cells. When compared to the cytotoxic effect with the chemotherapeutic drugs doxorubicin and cisplatin, C828 was found to be 20 times and 35 times more potent than doxorubicin and cisplatin, respectively. These results indicate that C828 could be a promising lead for developing new anticancer agents that target TNBC cells.

Crambescidin 800, Isolated from the Marine Sponge Monanchora viridis, Induces Cell Cycle Arrest and Apoptosis in Triple-Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is currently the only group of breast cancers without an effective targeted therapy. Marine sponges have historically been a source of compounds with anticancer activity. In this study, we screened extracts from twenty marine sponges collected off the coast of Western Australia for cytotoxic activity against TNBC cells. One very active extract derived from the sponge Monanchora viridis was selected for bioactivity-guided fractionation. Through multiple steps of purification, we isolated a potent cytotoxic compound, which was identified as crambescidin 800 (C800). We found that C800 exhibited cytotoxic potency in a panel of breast cancer cells, of which TNBC and luminal cancer cell models were the most sensitive. In addition, C800 induced cell cycle arrest at the G2/M phase, resulting in a decline in the expression of cyclin D1, CDK4, and CDK6 in TNBC cells. This effect was associated with the inhibition of phosphorylation of Akt, NF-κB, and MAPK pathways, resulting in apoptosis in TNBC cells.

Tri-µ-chlorido-bis-[(η(5)-penta-methyl-cyclo-penta-dien-yl)rhodium(III)] hexa-fluorido-phosphate from synchrotron radiation.

In the title complex salt, [{(η(5)-C5Me5)Rh}2(µ-Cl)3]PF6, the dinuclear, single-charged cation is formed by the cojoining of two classic (η(5)-C5Me5)RhCl3 'piano-stool' units by bridging of the three choride ligand 'legs'. The crystal structure shows several close H⋯F contacts between the hexa-fluorido-phosphate counter-ions and the C5Me5 ligands.

Macrocyclic bis(phenanthroline-pyrrole): a convenient one-pot synthesis, structure(s), spectroscopic, and redox properties, and the binding of amine guests, protons, and lanthanide ions.

This paper reports a convenient, one-pot, easily scalable and readily modifiable synthesis of a novel large-ring bis(1,10-phenanthrolinyl-2,5-pyrrole) macrocycle, H2LMC, and describes its spectroscopic and electrochemical properties, protonation, cooperative amine binding, electrocatalysis of the oxidation of primary amines, photosensitization of the decomposition of dichloromethane, and the first lanthanide complexes of the hexaaza-dianion LMC(2-) including the novel dimer, [(NO3)(LMC)Eu(µ-OH)Eu(LMC )(H2 O)2]·2py.

A dimer of bis-(N-heterocyclic carbene)rhodium(I) centres spanned by a dibenzo-18-crown-6 bridge from synchrotron radiation.

The compound (µ-3,3',3'',3'''-{[2,5,8,15,18,21-hexa-oxatricyclo-[20.4.0.0(9,14)]hexa-cosa-1(22),9,11,13,23,25-hexa-ene-11,12,24,25-tetra-yl]tetra-kis-(methyl-ene)}tetra-kis-(1-methyl-1H-imidazol-2-yl))bis-[(η(4)-cyclo-octa-1,4-diene)rhodium(I)] bis-(hexa-fluoridophosphate) acetonitrile sesquisolvate dihydrate, [Rh2(C8H12)2(C40H42N8O6)](PF6)2·1.5CH3CN·2H2O, crystallized from acetonitrile under an atmosphere of diethyl ether. In the crystal structure, the complex cation exhibits two square-planar Rh(I) centres, each bound by a cyclo-octa-diene (COD) ligand and by two adjacent imidazolyl-idene N-heterocyclic carbene (NHC) donors from the same phen-oxy ring of the {[dibenzo-18-crown-6-11,12,24,25-tetra-yl]tetra-kis-(methyl-ene)}tetra-kis-(1-methyl-1H-imidazol-2-yl) (L) ligand. The dibenzo-crown ether bridge of L spans the Rh centres and forms hydrogen bonds with water mol-ecules. One water mol-ecule with half occupancy bridges adjacent macrocycles in the lattice. Another water with full occupancy forms weak hydrogen bonds to the crown ether O atoms and is, in turn, part hydrogen bonded by a lattice water with half occupancy. The latter water is within hydrogen-bonding distance of a fourth water also with partial occupancy. The result of these inter-actions is the formation of a layer in the ab plane. Two PF6(-) ions, one of which is twofold disordered, and one ordered and one twofold disordered (with 0.5 occupancy) lattice acetonitrile mol-ecules complete the crystal structure.