Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6...Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.展开更多
OBJECTIVE:To investigate the therapeutic effect of Sishen Wan(四神丸,SSW)on ulcerative colitis(UC)induced by dinitrobenzene sulfonic acid and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase...OBJECTIVE:To investigate the therapeutic effect of Sishen Wan(四神丸,SSW)on ulcerative colitis(UC)induced by dinitrobenzene sulfonic acid and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB(TLR2/IRAK4/NF-κB)signaling pathway in colonic tissue.METHODS:In this study,120 Sprague–Dawley rats were randomly divided into blank and model groups.The experimental UC model in rats was established by subcutaneous injection of hydrocortisone+senna gavage for 21 d+dinitrobenzene sulfonic acid(DNBS)/ethanol solution enema.The successful model rats were randomly divided into the model group;mesalazine(0.36 g/kg)group;and high-,medium-,and low-dose SSW(24,12,and 6 g/kg)groups.The model and blank groups were gavaged with equal volumes of distilled water once a day for 21 d.The general condition of the rats was observed,and the body mass,fecal properties,and occult blood were recorded for calculating the disease activity index(DAI)score.The colonic tissue of the rats was collected,and its general morphology and pathological form were noted for obtaining the colonic mucosal injury index(CMDI)score.Hematoxylin-eosin staining was used to view the pathological changes of the colon tissue in each group,apoptosis of the cells was detected using terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling staining,and quantitative real-time polymerase chain reaction was used to measure the expressions of TLR2,myeloid differentiation primary response gene 88(My D88),IRAK4,and NF-κB p65 mRNA in the colon tissue.The expressions of TLR2,My D88,IRAK4,and NF-κB p65 protein were detected using western blotting and immunohistochemistry assay,and the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the colon tissue were determined using enzyme linked immunosorbent assay.RESULTS:Compared with the blank group,the general condition of the model group was relatively poor.The DAI and CMDI scores of the model group increased significantly(P<0.01),the glands and intestinal mucosa disappeared partially,and several inflammatory cells infiltrated and gathered in the mucosal layer and base layer of the rats in the model group.Furthermore,the cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of rats in the model group increased significantly(P<0.01).The levels of IL-1βand TNF-αincreased significantly in the colon tissue of rats in the model group(P<0.01).After treatment with SSW,compared with the model group,the general condition of the UC rats improved.Moreover,the DAI and CMDI scores of the UC rats decreased significantly(P<0.05),and the pathological changes in the colon tissue of the UC rats tended to be normal.The cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of the UC rats decreased gradually(P<0.01),and the levels of IL-1βand TNF-αdecreased significantly(P<0.01).CONCLUSION:SSW can improve the general condition and alleviate the intestinal mucosal injury of UC model rats.Additionally,SSW can inhibit the TLR2/IRAK4/NF-κB signaling pathway,but further studies are required to confirm it.展开更多
基金US National Institutes of Health(R01s AT007003,GM103437,GM71534,EY10208,GM49209)Unorthodox Philanthropy+3 种基金Open Philanthropythe Hickey Family Foundationthe Children’s Discovery InstituteWiley Companies。
文摘Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.
基金Supported by the National Natural Science Foundation of China:to Explore the Immune Mechanism of Treating Ulcerative Colitis by Regulating Treg/Th17 Cell Imbalance by Warming the Kidney and Invigorating the Spleen through Intestinal Flora(No.81960826)
文摘OBJECTIVE:To investigate the therapeutic effect of Sishen Wan(四神丸,SSW)on ulcerative colitis(UC)induced by dinitrobenzene sulfonic acid and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB(TLR2/IRAK4/NF-κB)signaling pathway in colonic tissue.METHODS:In this study,120 Sprague–Dawley rats were randomly divided into blank and model groups.The experimental UC model in rats was established by subcutaneous injection of hydrocortisone+senna gavage for 21 d+dinitrobenzene sulfonic acid(DNBS)/ethanol solution enema.The successful model rats were randomly divided into the model group;mesalazine(0.36 g/kg)group;and high-,medium-,and low-dose SSW(24,12,and 6 g/kg)groups.The model and blank groups were gavaged with equal volumes of distilled water once a day for 21 d.The general condition of the rats was observed,and the body mass,fecal properties,and occult blood were recorded for calculating the disease activity index(DAI)score.The colonic tissue of the rats was collected,and its general morphology and pathological form were noted for obtaining the colonic mucosal injury index(CMDI)score.Hematoxylin-eosin staining was used to view the pathological changes of the colon tissue in each group,apoptosis of the cells was detected using terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling staining,and quantitative real-time polymerase chain reaction was used to measure the expressions of TLR2,myeloid differentiation primary response gene 88(My D88),IRAK4,and NF-κB p65 mRNA in the colon tissue.The expressions of TLR2,My D88,IRAK4,and NF-κB p65 protein were detected using western blotting and immunohistochemistry assay,and the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the colon tissue were determined using enzyme linked immunosorbent assay.RESULTS:Compared with the blank group,the general condition of the model group was relatively poor.The DAI and CMDI scores of the model group increased significantly(P<0.01),the glands and intestinal mucosa disappeared partially,and several inflammatory cells infiltrated and gathered in the mucosal layer and base layer of the rats in the model group.Furthermore,the cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of rats in the model group increased significantly(P<0.01).The levels of IL-1βand TNF-αincreased significantly in the colon tissue of rats in the model group(P<0.01).After treatment with SSW,compared with the model group,the general condition of the UC rats improved.Moreover,the DAI and CMDI scores of the UC rats decreased significantly(P<0.05),and the pathological changes in the colon tissue of the UC rats tended to be normal.The cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of the UC rats decreased gradually(P<0.01),and the levels of IL-1βand TNF-αdecreased significantly(P<0.01).CONCLUSION:SSW can improve the general condition and alleviate the intestinal mucosal injury of UC model rats.Additionally,SSW can inhibit the TLR2/IRAK4/NF-κB signaling pathway,but further studies are required to confirm it.
