Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistoche...Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction （RT-PCR） and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma （MM patients） and peripheral blood mononuclear cells （PBMCs） obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations （5 to 320 μg/ml） for 24 h, and metabolic activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assays. Apoptosis was evaluated by dual Annexin V/Pl （propidium iodide） labeling and flow cytometry （FCM） in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results： By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^＋/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^＋/Pl^＋ cells. Conclusion： Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.展开更多
Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid...Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.展开更多
Microalgae Tetraselmis subcordiformis and Nannochloropsis oculata were cultured at 15,20,25,30,and 35℃ and their properties as potential biofuel resources were examined.The results indicate that T.subcordiformis and ...Microalgae Tetraselmis subcordiformis and Nannochloropsis oculata were cultured at 15,20,25,30,and 35℃ and their properties as potential biofuel resources were examined.The results indicate that T.subcordiformis and N.oculata grew best at 20℃ and 25℃ and yielded the highest total lipids at 20℃and 30℃,respectively.With increased temperature,neutral lipid and polyunsaturated fatty acids(FAs)decreased while saturated FAs increased,accompanied by increased monounsaturated FAs(MUFAs) in T.subcordiformis and decreased MUFAs in N.oculata;meanwhile,the predicted cetane number of FA methyl esters increased from 45.3 to 47.6 in T.subcordiformis and from 52.3 to 60.3 in N.oculata.Therefore,optimizing culture temperatures is important for improving microalgal biodiesel production.展开更多
基金Project supported by the Medicine and Health Research Fund of Zhejiang Province(No.2007B091)the Office of Education of Zhejiang Province,China(No.20070104)
文摘Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction （RT-PCR） and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma （MM patients） and peripheral blood mononuclear cells （PBMCs） obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations （5 to 320 μg/ml） for 24 h, and metabolic activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assays. Apoptosis was evaluated by dual Annexin V/Pl （propidium iodide） labeling and flow cytometry （FCM） in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results： By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^＋/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^＋/Pl^＋ cells. Conclusion： Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.
基金Supported by the National Marine Public Welfare Research Project(No.201305043)the National Natural Science Foundation of China(No.41106134)the National Key Technology R&D Program of China(Nos.2011BAD13B02,2010BAC68B01)
文摘Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.2009AA064401)the Special Fundation for Marine Renewable Energy from the State Oceanic Administration of China(No.SHME2011SW02)the Shanghai Universities First-class Disciplines Project of Fisheries(A)
文摘Microalgae Tetraselmis subcordiformis and Nannochloropsis oculata were cultured at 15,20,25,30,and 35℃ and their properties as potential biofuel resources were examined.The results indicate that T.subcordiformis and N.oculata grew best at 20℃ and 25℃ and yielded the highest total lipids at 20℃and 30℃,respectively.With increased temperature,neutral lipid and polyunsaturated fatty acids(FAs)decreased while saturated FAs increased,accompanied by increased monounsaturated FAs(MUFAs) in T.subcordiformis and decreased MUFAs in N.oculata;meanwhile,the predicted cetane number of FA methyl esters increased from 45.3 to 47.6 in T.subcordiformis and from 52.3 to 60.3 in N.oculata.Therefore,optimizing culture temperatures is important for improving microalgal biodiesel production.
