No abstract

Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson’s disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn2+ in human neuroblastoma SH-SY5Y cells. Mn2+ caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 μM Mn2+ (p <0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn2+ (2 μM, 62 μM or 125 μM). In addition, Mn2+ induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1 mM N-acetylcysteine or 1 mM glutathione reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that 1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA nucleotide base damage, 2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and 3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn2+-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants as a therapeutic strategy for protection against Mn2+-induced oxidative DNA damage.

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity.

Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicated that TQ was effective in reducing NO2- with an IC50 of 5.04 μM, relative to selective iNOS inhibitor LNIL- L-N6-(1-Iminoethyl)lysine (IC50 4.09 μM). TQ mediated reduction in NO2- was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In the next study, we evaluated the anti-inflammatory effects of TQ on ninety – six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin > MIP-1alpha > MIP-1g > IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine’s IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2 / MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA and mRNA expression profiling using RT2 Profiler PCR cytokine arrays. Moreover, the data obtained from the RT2 PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12 /MCP-5, CCL2 / MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.

BackgroundSince behavioral factors are significant determinants of population health, addressing prostate cancer (CaP)-related health beliefs and cultural beliefs are key weapons to fight this deadly disease. This study investigated the health beliefs and cultural beliefs of black men relative to CaP, and the key socio-demographic correlates of these beliefs.MethodsThe study design was a cross-sectional survey of 2,864 Florida black men, age 40 to 70, on their perceived susceptibility, perceived severity, attitude, outcomes beliefs, perceived behavioral control, CaP fatalism, religiosity, temporal orientation, and acculturation relative to CaP screening and prevention.ResultsThe men reported favorable attitude and positive outcome beliefs, but moderate perceived behavioral control, CaP susceptibility and CaP severity. They also had low level of acculturation, did not hold fatalistic beliefs about CaP, had high religious coping skills and had high future time perspective. Several demographic variables were found to be associated with health beliefs and cultural beliefs.DiscussionOur study provides rich data with regard to the health and cultural beliefs that might serve to inform the development of CaP control initiative for US-born and foreign-born black men.