Computational properties of η6-toluene and η6-trifluorotoluene half-sandwich Ru(II) anticancer complexes

The computational properties of the η6-toluene and η6-trifluorotoluene half-sandwich Ru(II) anticancer complexes and their respective hydrated complexes are computed using DFT method and the quantum theory of atoms in a molecule (QTAIM) analysis. The interatomic properties that are crucial in understanding the noncovalent interactions and the stability of these complexes are considered. We observed that high polarization, charge transfer (CT) and strong networks of intramolecular hydrogen bond (HB) interactions significant influenced the stability of these complexes. The trifluorotoluene and the hydrated models are characterized with higher CT, polarizability, synergistic effect of ligand fragments, stronger and higher HB interactions that support their reported experimental anticancer activities and the mechanism of their activation by hydrolysis. The complexes are predominantly characterized with metal to ligand CT.     

Priming of Production in Maize of Volatile Organic Defence Compounds by the Natural Plant Activator cis-Jasmone

cis-Jasmone (CJ) is a natural plant product that activates defence against herbivores in model and crop plants. In this study, we investigated whether CJ could prime defence in maize, Zea mays, against the leafhopper, Cicadulina storeyi, responsible for the transmission of maize streak virus (MSV). Priming occurs when a pre-treatment, in this case CJ, increases the potency and speed of a defence response upon subsequent attack on the plant. Here, we tested insect responses to plant volatile organic compounds (VOCs) using a Y-tube olfactometer bioassay. Our initial experiments showed that, in this system, there was no significant response of the herbivore to CJ itself and no difference in response to VOCs collected from unexposed plants compared to CJ exposed plants, both without insects. VOCs were then collected from C. storeyi-infested maize seedlings with and without CJ pre-treatment. The bioassay revealed a significant preference by this pest for VOCs from infested seedlings without the CJ pre-treatment. A timed series of VOC collections and bioassays showed that the effect was strongest in the first 22 h of insect infestation, i.e. before the insects had themselves induced a change in VOC emission. Chemical analysis showed that treatment of maize seedlings with CJ, followed by exposure to C. storeyi, led to a significant increase in emission of the defensive sesquiterpenes (E)-(1R,9S)-caryophyllene, (E)-α-bergamotene, (E)-β-farnesene and (E)-4,8-dimethyl-1,3,7-nonatriene, known to act as herbivore repellents. The chemical analysis explains the behavioural effects observed in the olfactometer, as the CJ treatment caused plants to emit a blend of VOCs comprising more of the repellent components in the first 22 h of insect infestation than control plants. The speed and potency of VOC emission was increased by the CJ pre-treatment. This is the first indication that CJ can prime plants for enhanced production of defensive VOCs antagonist towards herbivores.     

Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations

Circulating tumor cells (CTCs) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique(s) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional (3D) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability (CIN) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.     

Biodegradation of anthracene by a novel actinomycete, Microbacterium sp. isolated from tropical hydrocarbon-contaminated soil

A novel anthracene-degrading Gram-positive actinomycete, Microbacterium sp. strain SL10 was isolated from a hydrocarbon-contaminated soil at a mechanical engineering workshop in Lagos, Nigeria. The polluted soil had an unusually high total hydrocarbon content of 157 g/kg and presence of various heavy metals. The isolate tolerated salt concentration of more than 4 %. It resisted cefotaxime, streptomycin and ciprofloxacin, but susceptible to meropenem, linezolid and vancomycin. The isolate exhibited growth rate and doubling time of 0.82 days^-1 and 0.84 days, respectively on anthracene. It degraded 57.5 and 90.12 % of anthracene within 12 and 21 days, respectively while the rate of anthracene utilization by the isolate was 4.79 mg l^-1 d^-1. To the best of our knowledge, this is the first report of isolation and characterization of anthracene-degrading Microbacterium sp.     

Comparative study on the influence of fluoride on lipid peroxidation and antioxidants levels in the different brain regions of well-fed and protein undernourished rats

Effects of fluoride on the levels of Lipid peroxidation (LP) and antioxidant enzymes in the brain regions of protein undernourished (PU) and well-fed rats (WF) rats exposed to 100 ppm fluoride in drinking water were investigated. The results indicate that the mean body weights and the total brain weights of PU rats as well as those given fluoride (both WF and PU) were significantly (P < 0.05) lower than their respective controls. The weights of different brain regions were also significantly reduced (P < 0.05) in PU rats compared to WF rats except in the brain stem. Fluoride ingestion diminished the weights of WF and PU rats affecting the cerebrum only (in the case of PU rats) and the cerebellum of both WF and PU rats without an effect on the brain stem of both WF and PU. Additionally, increased LP was observed in the cerebrum and cerebellum of PU rats but after fluoride ingestion, 30% increase in LP was observed only in the cerebrum. In the brain stem however, protein undernutrition was accompanied with a significant reduction in LP but the region seems insensitive to fluoride. There were significant reductions (P < 0.05) in CAT, SOD and GSH in all the brain regions (except the GSH level in the brain stem only) of PU rats. Fluoride induced reduction in the activity of CAT in the three brain regions and on SOD activity in cerebrum only for WF rats but no effect of fluoride on all the antioxidants studied in the three brain regions for PU rats. It is concluded that WF and PU rats responded differently to fluoride toxicity. However, it seems that at the dosage used, fluoride toxicity may be a direct effect on the antioxidant enzymes.     

Serum concentrations of immunoglobulins and acute phase proteins in Nigerian women with preeclampsia

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed based on a triad of hypertension, significant proteinuria and rapidly increasing edema during gestation. The factors that initiate preeclampsia are unknown and still a subject of intense clinical research. The objective of this study is to provide additional immunological information about preeclampsia. To achieve this, humoral immunochemical parameters such as three classes of immunoglobulin (IgA, IgG and IgM) and three acute phase proteins (alpha 2-macroglobulin, haptoglobin and transferrin) were measured by single radial immunodifussion method in 32 pregnant women with preeclampsia, 36 pregnant women without preeclampsia and 24 non-pregnant women (controls). Total protein in the urine was also determined by spectrophotometric method. In women with preeclampsia, the levels of IgG, IgA, transferrin and alpha 2-macroglobulin were significantly reduced compared with subjects with normal pregnancy, but the level of haptoglobin was significantly raised in preeclampsia compared with women having normal pregnancy. Urinary total protein and IgG were significantly raised in Nigerian women with preeclampsia compared with non-pregnant controls. There were significant negative correlations between serum IgG, IgA and urinary protein. The possible involvement of immunoglobulins and acute phase proteins in preeclampsia is discussed.     

Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion

We examined the effect of Niemann-Pick disease type 2 (NPC2) protein and some late endosomal lipids [sphingomyelin, ceramide and bis(monoacylglycero)phosphate (BMP)] on cholesterol transfer and membrane fusion. Of all lipid-binding proteins tested, only NPC2 transferred cholesterol at a substantial rate, with no transfer of ceramide, GM3, galactosylceramide, sulfatide, phosphatidylethanolamine, or phosphatidylserine. Cholesterol transfer was greatly stimulated by BMP, little by ceramide, and strongly inhibited by sphingomyelin. Cholesterol and ceramide were also significantly transferred in the absence of protein. This spontaneous transfer of cholesterol was greatly enhanced by ceramide, slightly by BMP, and strongly inhibited by sphingomyelin. In our transfer assay, biotinylated donor liposomes were separated from fluorescent acceptor liposomes by streptavidin-coated magnetic beads. Thus, the loss of fluorescence indicated membrane fusion. Ceramide induced spontaneous fusion of lipid vesicles even at very low concentrations, while BMP and sphingomyelin did so at about 20 mol% and 10 mol% concentrations, respectively. In addition to transfer of cholesterol, NPC2 induced membrane fusion, although less than saposin-C. In this process, BMP and ceramide had a strong and mild stimulating effect, and sphingomyelin an inhibiting effect, respectively. Note that the effects of the lipids on cholesterol transfer mediated by NPC2 were similar to their effect on membrane fusion induced by NPC2 and saposin-C.     

The effects of point of substitution on the electrochemical behavior of new manganese phthalocyanines, tetra-substituted with diethylaminoethanethiol

The syntheses and comparative studies of the spectral, voltammetry and spectroelectrochemical properties of new manganese phthalocyanine complexes, tetra-substituted with diethylaminoethanethio at the peripheral (complex 3a) and non-peripheral positions (complex 3b) are reported. Solution electrochemistry of complex 3a showed quasi-reversible metal-based (Mn^IIIPc⁻²/Mn^IIPc⁻², E_1/2 = −0.07 V vs. Ag|AgCl) and ring-based (Mn^IIPc⁻²/Mn^IIPc⁻³, E_1/2 = −0.78 V vs. Ag|AgCl) reductions, but no ring-based oxidation. However, complex 3b showed weak irreversible ring-oxidation signal (E_p = +0.86 vs. Ag|AgCl). Reversible metal-based (Mn^IIIPc⁻²/Mn^IIPc⁻², E_1/2 = −0.04 V vs. Ag|AgCl) and ring-based (Mn^IIPc⁻²/Mn^IIPc⁻³, E_1/2 = −0.68 V vs. Ag|AgCl) reductions were also observed for complex 3b. Spectroelectrochemistry was used to confirm these processes. Reduction process involving the metal (Mn^IIIPc⁻²/Mn^IIPc⁻²) was associated with the formation of manganese μ-oxo complex in complex 3a.     

NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR)α-mediated cardiovascular effects

Activation of peroxisome proliferator activated receptor (PPAR)α and its protective role in cardiovascular function has been reported but the exact mechanism(s) involved is not clear. As we have shown that PPARα ligands increased nitric oxide (NO) production and cardiovascular function is controlled by a balance between NO and free radicals, we hypothesize that PPARα activation tilts the balance between NO and free radicals and that this mechanism defines the protective effects of PPARα ligands on cardiovascular system. Systolic blood pressure (SBP) was greater in PPARα knockout (KO) mice compared with its wild type (WT) litter mates (130 ± 10 mmHg versus 107 ± 4 mmHg). l-NAME (100 mg/L p.o.), the inhibitor of NO production abolished the difference between PPARα KO and WT mice. In kidney homogenates, tissue lipid hydroperoxide generation was greater in KO mice (11.8 ± 1.4 pM/mg versus 8.3 ± 0.6 pM/mg protein). This was accompanied by a higher total NOS activity (46 ± 6%, p < 0.05) and a 3 fold greater Ca²⁺-dependent NOS activity in kidney homogenates of untreated PPARα WT compared with the KO mice. Clofibrate, a PPARα ligand, increased NOS activity in WT but not KO mice. Bezafibrate (30 mg/kg) reduced SBP in conscious rats (19 ± 4%, p < 0.05), increased urinary NO excretion (4.06 ± 0.53–7.07 ± 1.59 μM/24 h; p < 0.05) and reduced plasma 8-isoprostane level (45.8 ± 15 μM versus 31.4 ± 8 μM), and NADP(H) oxidase activity (16 ± 5%). Implantation of DOCA pellet (20 mg s.c.) in uninephrectomized mice placed on 1% NaCl drinking water increased SBP by a margin that was markedly greater in KO mice (193 ± 13 mmHg versus 130 ± 12 mmHg). In the rat, DOCA increased SBP and NAD(P)H oxidase activity and both effects were diminished by clofibrate. In addition, clofibrate reduced ET-1 production in DOCA/salt hypertensive rats. Thus, apart from inhibition of ET-1 production, PPARα activation exerts protective actions in hypertension via a mechanism that involves NO production and/or inhibition of NAD(P)H oxidase activity.