Polyunsaturated fatty acids （PUFAs） are essential for normal growth in mammals, especially the ω-3 PUFAs, which play important roles in preventing several life-threatening diseases, such as coronary heart disease a...Polyunsaturated fatty acids （PUFAs） are essential for normal growth in mammals, especially the ω-3 PUFAs, which play important roles in preventing several life-threatening diseases, such as coronary heart disease and diabetes. In this study, we aimed to investigate whether the sFat-1 gene from Caenorhabditis briggsae could be functionally expressed in transgenic pigs, and whether the transgenic could synthesize high quality ω-3 PUFAs endogenously. In this study, a gene construct consisting of CMV promoter and 1.9 kb cDNA of ω-3 fatty acid desaturase gene （sFat-1） from C. briggsae was injected into the male pronucleus of pig embryos by microinjection. The piglets were screened for the transgene by PCR, Southern blot and reverse transcription-PCR analysis. Pigs that give positive results were mated with wild-type pigs to produce the next generation and the transmission of transgene was examined by PCR analysis. Fatty acids compositions of various tissues in the transgenic pigs were then analyzed by gas chromatograph. A total of 878 embryos were transferred into 42 recipients, among which 29 successfully got pregnant and gave birth to a total of 162 piglets, and 8 of them were identified to be transgenic. Fatty acid compositions in the transgenic pigs were altered, and the levels of ω-6：ω-3 ratios were decreased from 14.53 in the control to 2.62 in Fat-1 transgenic pigs. A number of primary sFat-1-transgenic pigs were bred in this study, which lays the foundation for cultivation of new varieties of transgenic pigs.展开更多
AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 5...AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.展开更多
AIM： To assess the value of long-chain w-3 fatty acids （FAs） supplementation in addition to amino-salicylic-acid （5-ASA） in pediatric patients with Crohn＇s disease （CD）. METHODS： Thirty-eight patients （20 ma...AIM： To assess the value of long-chain w-3 fatty acids （FAs） supplementation in addition to amino-salicylic-acid （5-ASA） in pediatric patients with Crohn＇s disease （CD）. METHODS： Thirty-eight patients （20 males and 18 females, mean age 10.13 years, range 5-16 years） with CD in remission were randomized into two groups and treated for 12 too. Group Ⅰ （18 patients） received 5-ASA （50 mg/kg/d）＋w-3 FAs as triglycerides in gastroresistant capsules, 3 g/d （eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g）. Group Ⅱ （20 patients） received 5-ASA （50 mg/kg/d）＋olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS： The number of patients who relapsed at 1 year was significantly lower in group I than in group Ⅱ （P〈0.001）. Patients in group I had a significant increase in the incorporation of EPA and DHA （P〈0.001） and a decrease in the presence of arachidonic acids. CONCLUSION： Enteric-coated w-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD.展开更多
This study examined the effects of ω-3 polyunsaturated fatty acid（ω-3PUFA） on the expression of toll-like receptor 2（TLR2）,toll-like receptor 4（TLR4） and some related inflammatory factors in peripheral blood m...This study examined the effects of ω-3 polyunsaturated fatty acid（ω-3PUFA） on the expression of toll-like receptor 2（TLR2）,toll-like receptor 4（TLR4） and some related inflammatory factors in peripheral blood mononuclear cells（PBMCs） of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital（Wuhan,China） between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score（ISS） no less than 16,were enrolled in the study and divided into two groups at random（n=16 in each）：ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission（day 0）,and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support（both P0.05）.The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day（P0.05 for all）.It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.展开更多
Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an in...Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an inverse association between n - 3 intake and human cancers. However, n - 3 are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy from fat) with or without an additional 3% of energy from a mixture of n - 3 (with 5.36 g α-linolenic acid and 1.45 g eicosapentaenoic acid and docosahexaenoic acid per 2000 kcal per day), we measured total in vivo lipid peroxidation in healthy postmenopausal women (n = 15). Our results indicated that the diet with 3% of energy from n - 3 significantly increased the urinary concentrations of total polar lipophilic aldehydes and related compounds produced via lipid peroxidation (p α, β-unsaturated hydroxy aldehydes 4-hydroxy-2-trans - hexenal (p trans -decenal (p < 0.05) compared to the diet with less than 1% of energy from n - 3. This is also the first study to document the presence of 4-hydroxy-2-trans -decenal in the urine of individuals consuming n - 3. These results demonstrate that an increase in 3% of energy from dietary n – 3 increases in vivo lipid peroxidation.展开更多
Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excess...Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excessive LA on colon cancer in human is not conclusive,making it difficult to make dietary recommendations for optimal intake of LA.Understanding the molecular mechanisms of LA on colon tumorigenesis could help to clarify its health effect,and facilitate development of mechanismbased strategies for preventing colon cancer.Recent studies show that the previously unappreciated cytochrome P450 monooxygenase-mediated eicosanoid pathway is upregulated in colon cancer and plays critical roles in its pathogenesis,and could contribute to the effects of dietary LA,as well asω-3 fatty acids,on colon tumorigenesis.In this review,we will discuss recent studies about the roles of cytochrome P450 monooxygenases in fatty acid metabolism and its roles in colonic inflammation and colon cancer,and how this information could help us to clarify the health impacts of dietary fatty acids.展开更多
基金supported by the National Transgenic Breeding Project, China (2008ZX08010-004)the National Natural Science Foundation of China (30830080)+1 种基金the National Basic Research Program of China (G2006CB102105, 2009CB941604)the National High Technology Research and Development Program of China (20060110Z1039, 2008AA10Z143)
文摘Polyunsaturated fatty acids （PUFAs） are essential for normal growth in mammals, especially the ω-3 PUFAs, which play important roles in preventing several life-threatening diseases, such as coronary heart disease and diabetes. In this study, we aimed to investigate whether the sFat-1 gene from Caenorhabditis briggsae could be functionally expressed in transgenic pigs, and whether the transgenic could synthesize high quality ω-3 PUFAs endogenously. In this study, a gene construct consisting of CMV promoter and 1.9 kb cDNA of ω-3 fatty acid desaturase gene （sFat-1） from C. briggsae was injected into the male pronucleus of pig embryos by microinjection. The piglets were screened for the transgene by PCR, Southern blot and reverse transcription-PCR analysis. Pigs that give positive results were mated with wild-type pigs to produce the next generation and the transmission of transgene was examined by PCR analysis. Fatty acids compositions of various tissues in the transgenic pigs were then analyzed by gas chromatograph. A total of 878 embryos were transferred into 42 recipients, among which 29 successfully got pregnant and gave birth to a total of 162 piglets, and 8 of them were identified to be transgenic. Fatty acid compositions in the transgenic pigs were altered, and the levels of ω-6：ω-3 ratios were decreased from 14.53 in the control to 2.62 in Fat-1 transgenic pigs. A number of primary sFat-1-transgenic pigs were bred in this study, which lays the foundation for cultivation of new varieties of transgenic pigs.
基金Supported by Jinling Hospital Research Fund,No.2013064
文摘AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.
文摘AIM： To assess the value of long-chain w-3 fatty acids （FAs） supplementation in addition to amino-salicylic-acid （5-ASA） in pediatric patients with Crohn＇s disease （CD）. METHODS： Thirty-eight patients （20 males and 18 females, mean age 10.13 years, range 5-16 years） with CD in remission were randomized into two groups and treated for 12 too. Group Ⅰ （18 patients） received 5-ASA （50 mg/kg/d）＋w-3 FAs as triglycerides in gastroresistant capsules, 3 g/d （eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g）. Group Ⅱ （20 patients） received 5-ASA （50 mg/kg/d）＋olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS： The number of patients who relapsed at 1 year was significantly lower in group I than in group Ⅱ （P〈0.001）. Patients in group I had a significant increase in the incorporation of EPA and DHA （P〈0.001） and a decrease in the presence of arachidonic acids. CONCLUSION： Enteric-coated w-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD.
基金supported by a grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China (No. 2009-1001)
文摘This study examined the effects of ω-3 polyunsaturated fatty acid（ω-3PUFA） on the expression of toll-like receptor 2（TLR2）,toll-like receptor 4（TLR4） and some related inflammatory factors in peripheral blood mononuclear cells（PBMCs） of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital（Wuhan,China） between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score（ISS） no less than 16,were enrolled in the study and divided into two groups at random（n=16 in each）：ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission（day 0）,and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support（both P0.05）.The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day（P0.05 for all）.It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.
文摘Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an inverse association between n - 3 intake and human cancers. However, n - 3 are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy from fat) with or without an additional 3% of energy from a mixture of n - 3 (with 5.36 g α-linolenic acid and 1.45 g eicosapentaenoic acid and docosahexaenoic acid per 2000 kcal per day), we measured total in vivo lipid peroxidation in healthy postmenopausal women (n = 15). Our results indicated that the diet with 3% of energy from n - 3 significantly increased the urinary concentrations of total polar lipophilic aldehydes and related compounds produced via lipid peroxidation (p α, β-unsaturated hydroxy aldehydes 4-hydroxy-2-trans - hexenal (p trans -decenal (p < 0.05) compared to the diet with less than 1% of energy from n - 3. This is also the first study to document the presence of 4-hydroxy-2-trans -decenal in the urine of individuals consuming n - 3. These results demonstrate that an increase in 3% of energy from dietary n – 3 increases in vivo lipid peroxidation.
基金This research is supported by a new faculty start-up from the University of Massachusetts Amherst,USDA NIFA2016-67017-24423,USDA NIFA 2019-67017-29248,USDA/HatchMAS00492,and NIH/NCIR03 CA218520(to G.Z.).
文摘Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excessive LA on colon cancer in human is not conclusive,making it difficult to make dietary recommendations for optimal intake of LA.Understanding the molecular mechanisms of LA on colon tumorigenesis could help to clarify its health effect,and facilitate development of mechanismbased strategies for preventing colon cancer.Recent studies show that the previously unappreciated cytochrome P450 monooxygenase-mediated eicosanoid pathway is upregulated in colon cancer and plays critical roles in its pathogenesis,and could contribute to the effects of dietary LA,as well asω-3 fatty acids,on colon tumorigenesis.In this review,we will discuss recent studies about the roles of cytochrome P450 monooxygenases in fatty acid metabolism and its roles in colonic inflammation and colon cancer,and how this information could help us to clarify the health impacts of dietary fatty acids.
