Transcriptome profile of rat genes in bone marrow-derived macrophages at different activation statuses by RNA-sequencing.

The underlying mechanisms of macrophage polarization have been detected by genome-wide transcriptome analysis in a variety of mammals. However, the transcriptome profile of rat genes in bone marrow-derived macrophages (BMM) at different activation statuses has not been reported. Therefore, we performed RNA-Sequencing to identify gene expression signatures of rat BMM polarized in vitro with different stimuli. The differentially expressed genes (DEGs) among unactivated (M0), classically activated pro-inflammatory (M1), and alternatively activated anti-inflammatory macrophages (M2) were analyzed by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In this study, not only we have identified the changes of global gene expression in rat M0, M1 and M2, but we have also made clear systematically the key genes and signaling pathways in the differentiation process of M0 to M1 and M2. These will provide a foundation for future researches of macrophage polarization.

Expression and Cellular Localization of IFITM1 in Normal and Injured Rat Spinal Cords.

Interferon-induced transmembrane protein 1 (IFITM1) is a member of the IFITM family that is associated with some acute-phase cytokine-stimulated response. Recently, we demonstrated that IFITM1 was significantly upregulated in the injured spinal cords at the mRNA level. However, its expression and cellular localization at the protein level is still unclear. Here, a rat model of spinal cord injury (SCI) was performed to investigate the spatio-temporal expression of IFITM1 after SCI. IFITM1 mRNA and protein were assessed by quantitative reverse transcription-PCR and western blot, respectively. IHC was used to identify its cellular localization. We revealed that IFITM1 could be found in sham-opened spinal cords and gradually increased after SCI. It reached peak at 7 and 14 days postinjury (dpi) and still maintained at a relatively higher level at 28 dpi. IHC showed that IFITM1 expressed in GFAP+ and APC+ cells in sham-opened spinal cords. After SCI, in addition to the above-mentioned cells, it could also be found in CD45+ and CD68+ cells, and its expression in CD45+, CD68+, and GFAP+ cells was increased significantly. These results demonstrate that IFITM1 is mainly expressed in astrocytes and oligodendroglia in normal spinal cords, and could rapidly increase in infiltrated leukocytes, activated microglia, and astrocytes after SCI.

Methyl mercury, but not inorganic mercury, associated with higher blood pressure during pregnancy.

Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross-sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n-3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n-3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40µg/L (95% confidence interval: 1.29, 1.52); 0.95µg/L (0.84, 1.07); and 0.13µg/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one-tertile increase of methyl mercury was associated with 2.83mmHg (0.17, 5.50) higher systolic blood pressure and 2.99mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with -1.18mmHg (-3.72, 1.35) lower systolic blood pressure and -2.51mmHg (-4.49, -0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non-significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies.

Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex.

BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. OBJECTIVE: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. METHODS: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). RESULTS: Geometric mean cord blood MeHg was 0.94 µg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, ßln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, ßln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, ßln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, ßln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, ßln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, ßln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). CONCLUSION: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.

Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and promotes weight gain in mice fed a low fat diet.

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.

Body burdens of mercury, lead, selenium and copper among Baltimore newborns.

Umbilical cord blood or serum concentrations of mercury, lead, selenium and copper were measured with inductively coupled plasma mass spectrometry in a population of 300 infants born in Baltimore, Maryland. Geometric mean values were 1.37 µg/L (95% confidence interval: 1.27, 1.48) for mercury; 0.66 µg/dL (95% CI: 0.61, 0.71) for lead; and 38.62 µg/dL (95% CI: 36.73, 40.61) for copper. Mean selenium was 70.10 µg/L (95% CI: 68.69, 70.52). Mercury, selenium and copper levels were within exposure ranges reported among similar populations, whereas the distribution of lead levels was lower than prior reports; only one infant had a cord blood lead above 10 µg/dL. Levels of selenium were significantly correlated with concentrations of lead (Spearman's ρ=0.20) and copper (Spearman's ρ=0.51). Multivariable analyses identified a number of factors associated with one of more of these exposures. These included: increase in maternal age (increased lead); Asian mothers (increased mercury and lead, decreased selenium and copper); higher umbilical cord serum n-3 fatty acids (increased mercury, selenium and copper), mothers using Medicaid (increased lead); increasing gestational age (increased copper); increasing birthweight (increased selenium); older neighborhood housing stock (increased lead and selenium); and maternal smoking (increased lead). This work provides additional information about contemporary prenatal element exposures and can help identify groups at risk of atypical exposures.