Modification of Marine Natural Product Ningalin B and SAR Study Lead to Potent P-Glycoprotein Inhibitors

In this study, new marine ningalin B analogues containing a piperazine or a benzoloxy group at ring C have been synthesized and evaluated on their P-gp modulating activity in human breast cancer and leukemia cell lines. Their structure-activity relationship was preliminarily studied. Compounds 19 and 20 are potent P-gp inhibitors. These two synthetic analogues of permethyl ningalin B may be potentially used as effective modulators of P-gp-mediated drug resistance in cancer cells.     

外源硝态氮对菊芋耐海水胁迫的影响

A hydroponic experiment with six treatments, i.e., 0% seawater （control）, 10% seawater, 25% seawater, 0% seawater ＋ N （7.5 mmol L-1 NaNO3）, 10% seawater ＋ N （7.5 mmol L-1 NaO3）, and 25% seawater ＋ N （7.5 mmol L-1 NaNO3）, was carried out to study the effect of nitrogen addition on the growth and physiological and biochemical characteristics of Jerusalem artichoke （Helianthus tuberosus） seedlings under seawater stress. The 10% seawater stress treatment had the least effect on plant growth while at 25% seawater growth was significantly inhibited. The malondialdehyde content and electrolyte leakage in leaves under 10% seawater were similar to those of the control, but significantly higher under the 25% seawater stress. The activities of superoxide dismutase, peroxidase and catalase in the leaves increased concomitantly with increasing seawater concentration and time. Proline and soluble-sugars in the leaves and Na^＋, K^＋, and Cl- contents in shoots and roots increased significantly with the concentration of seawater increasing. Nitrogen addition resulted in increasing fresh and dry weights of shoots and roots compared with seawater treatment without N. Nitrogen supplementation also significantly enhanced the activities of antioxidant enzymes in leaves. Addition of N to seawater enhanced the contents of proline and soluble-sugars in the leaves and K^＋ and total-N in the aerial parts and roots of H. tuberosus, but it resulted in declined concentrations of Na^＋ and Cl- in the aerial parts and roots. Nitrogen addition ameliorated the toxicity of seawater by improving the antioxidative enzymes, accumulating of proiine and soluble-sugars, and altering the distribution of inorganic ions in H. tuberosus.     

Detection of bovine viral diarrhea virus (BVDV) in seropositive cattle

Detection of bovine virus diarrhoea virus (BVDV) in one vaccinated beef cattle and three non-vaccinated dairy herds was investigated on peripheral blood leukocytes (PBL) with or without previous treatment followed by a capture ELISA (cELISA). Using the combination of PHA and polycation treatment, PBL from 229 seropositive cattle were studied and could be classified in four different states of BVDV infection. Lysed PBL from four animals were directly positive in cELISA (Category I), PBL of 17 animals were positive after PHA stimulation (Category II), 15 animals were positive only after PHA stimulation plus polycation treatment (Category III), while virus could not be detected in 193 seropositive cattle. Wild-type BVDV strains were isolated by co-culture on polycation-treated MDBK cells from 11 of these seropositive animals. BVDV antibodies of these same animals were able to neutralize their own virus, indicating that virus persists in PBL in spite of strain-specific antibodies. No apparent change of leukocyte subpopulations could be detected in any category of virus-positive animals. Thus, BVDV may be present in the PBL of some cattle, even in the presence of a specific active immune response.     

Immune response of pregnant cows to bovine rotavirus immunization

Fifteen pregnant Holstein cows were freely assigned to 3 experimental groups (5 cows in each group). Cows in group I were inoculated IM and intramammarily (IMm) with Ohio Agricultural Research and Development Center (OARDC) tissue culture-propagated modified-live Nebraska calf diarrhea bovine rotavirus with added adjuvant (OARDC vaccine-immunized cows). Group II cows were given IM injections of a commercial modified-live rotavirus-coronavirus vaccine (commercial vaccine-immunized cows), and the remaining 5 cows were noninoculated controls (group III). Rotavirus antibody in colostrum and milk was mainly associated with immunoglobulin (Ig)G1, and less so with IgG2, IgA, and IgM, as analyzed by the enzyme-linked immunosorbent assay (ELISA), using monospecific anti-bovine IgG1, IgG2, IgM, and IgA sera. In serum, the rotavirus antibody was distributed almost equally between IgG1 and IgG2. The same relationships appeared in both immunized and nonvaccinated cows. All OARDC vaccine-injected cows had virus-neutralization (VN) and ELISA IgG1 rotavirus antibody titers in serum and mammary secretions at significantly increased levels (at least 100-fold; P less than 0.05) compared with the titers in groups II (commercial vaccine-immunized cows) and III (controls). Serum, colostrum, and milk antibody titers from these latter 2 groups did not differ statistically. The ELISA IgG2, IgA, and IgM rotavirus antibody titers also were significantly greater in mammary secretions from OARDC vaccine-immunized cows than in groups II and III cows. There was a high correlation between ELISA IgG1 and VN rotavirus antibody titers for all samples tested (r = 0.97, P less than 0.001), but ELISA IgG1 antibody titers were consistently higher than VN titers. The ELISA IgG1 and VN antibody titers of milk samples collected from cows 30 days after parturition were higher from the OARDC vaccine-immunized cows (ELISA IgG1, geometric mean titer (GMT) = 3,511; VN GMT = 1,689) than were titers from the group II cows (ELISA IgG1 GMT = 39; VN GMT = 33) or group III cows (ELISA IgG1 GMT = 21; VN GMT = 19). These results indicate that IM plus IMm immunization of pregnant cows, using modified-live bovine rotavirus with added adjuvant, may significantly enhance serum, colostrum, and milk rotavirus antibody titers, whereas IM vaccinal inoculation of pregnant cows with a commercial modified-live rotavirus-coronavirus vaccine may not.     

Calcium, diet and fracture risk: a prospective study of 1898 incident fractures among 34 696 British women and men

OBJECTIVE: The risk factors for fractures are incompletely understood. An outstanding question concerns the optimal amount of dietary calcium needed to minimise the risk of fracture. DESIGN: We examined the associations of dietary calcium and other nutrients with self-reported fracture risk in a prospective cohort study. Nutrient intakes were estimated using a semi-quantitative food-frequency questionnaire administered at recruitment. SETTING: The UK. Participants: A total of 26 749 women and 7947 men aged 20-89 years. RESULTS: Over an average of 5.2 years of follow-up, 1555 women and 343 men reported one or more fractures, 72% of these resulting from a fall. Among women, fracture risk was higher at lower calcium intakes, with a relative risk of 1.75 (95% confidence interval (CI) 1.33-2.29) among women with a calcium intake of < 525 mg day- 1 compared with women with a calcium intake of at least 1200 mg day- 1 (test for linear trend, P < 0.001). The association of dietary calcium with fracture risk was stronger among women aged under 50 years at recruitment than among women aged 50 and above. Dietary calcium intake was not associated with fracture risk in men. Fracture risk was not related to the dietary intake of any other nutrient examined. CONCLUSION: In this population, women with a low dietary calcium intake had an increased risk of bone fracture, and this association was more marked among younger women than among older women.     

Effect of dietary Schizochytrium microalga oil and fish oil on plasma cholesterol level in rats

The purpose of the study was to test the hypothesis that the dietary oils with different content of n‐3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) affect plasma lipid level in rats in a different degree. The diets with 6% of fish oil (FO) and Schizochytrium microalga oil (SchO; EPA+DHA content in the diets 9.5 + 12.3 and 2.6 + 29.5% of the sum of total fatty acids, respectively) were used; the diet with 6% of safflower oil (high content of n‐6 PUFA linoleic acid, 65.5%; EPA+DHA content 0.7 + 0.9%) was used as a control. The difference between FO and SchO was established only in the case of plasma triacylglycerol (TAG) level: plasma TAG of the FO‐fed rats did not differ from the control rats (p > 0.05), while SchO decreased (p < 0.05) plasma TAG to 46% of the control. On the other hand, FO and SchO decreased (p < 0.05) total plasma cholesterol (TC) in rats in the same extent, to 73% of the control. Regarding the underlying mechanisms for the TC decrease, both SchO and FO up‐regulated hepatic Insig‐1 gene (181 and 133% of the control; p < 0.05), which tended (p = 0.15 and p = 0.19 respectively) to decrease the amount of hepatic nSREBP‐2 protein (61 and 66% of the control). However, neither SchO nor FO influenced hepatic 3‐hydroxy‐3‐methyl‐glutaryl‐CoA reductase gene expression (p > 0.05); SchO (but not FO) increased (p < 0.05) low‐density lipoprotein receptor mRNA in the liver. It was concluded that the decrease of total plasma cholesterol might be caused by an increased cholesterol uptake from plasma into the cells (in the case of SchO), but also by other (in the present study not tested) mechanisms.