Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous socia...Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.展开更多
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
The physical model describing the Yin-Yang balance in the Tai-chi diagram via the melting and freezing processes taking place in a rotating device presented in reference [1] is further developed. The system of equatio...The physical model describing the Yin-Yang balance in the Tai-chi diagram via the melting and freezing processes taking place in a rotating device presented in reference [1] is further developed. The system of equations formulating the melting and freezing processes is transformed to a dimensionless form. The advantage of dimensionless equations not only reduces a significant number of parameters involved in the problem but also provides physical insight of the Tai-chi diagram. The solution of dimensionless equations offers the similarity and characteristic of the Tai-chi diagram[1].展开更多
Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HI...Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches.Methods:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 interventions.We generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production.Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production.In addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with HIV-1.Results:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host optima.In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic targets.In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.展开更多
Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted co...Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted considerable attention for its combined effect.VSL#3 is the only probiotic considered as a kind of medical food;it mainly participates in the regulation of the intestinal barrier function,including improving tight junction protein function,balancing intestinal microbial composition,regulating immune-related cytokine expression and so on.The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans(including children).We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies,including digestive systemic diseases(gastrointestinal diseases and hepatic diseases),obesity and diabetes,allergic diseases,nervous systemic diseases,atherosclerosis,bone diseases,and female reproductive systemic diseases.展开更多
基金supported in part by the New York State Office of People with Developmental Disabilities(OPWDD)Zenith Award ZEN-12-241233 from Alzheimer’s Associationa research grant#20121203 from Alzheimer’s Drug Discovery Foundation,New York
文摘Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.
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The present work is being supported by the Natural Sciences Engineering Research Council of Canada under Grant No. OGP0007929.
文摘The physical model describing the Yin-Yang balance in the Tai-chi diagram via the melting and freezing processes taking place in a rotating device presented in reference [1] is further developed. The system of equations formulating the melting and freezing processes is transformed to a dimensionless form. The advantage of dimensionless equations not only reduces a significant number of parameters involved in the problem but also provides physical insight of the Tai-chi diagram. The solution of dimensionless equations offers the similarity and characteristic of the Tai-chi diagram[1].
基金the National Natural Science Foundation of China(82071784)the Fundamental Research Funds for the Central Universities(2042022dx0003 and PTPP2023002)+1 种基金the Key Research and Development Project of Hubei Province(2020BCA069)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202007).
文摘Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches.Methods:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 interventions.We generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production.Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production.In addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with HIV-1.Results:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host optima.In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic targets.In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.
基金the Innovative Talent Support Program of the Institution of Higher Learning in Liaoning Province,No.2018-478the Innovative Talents of Science and Technology Support Program of Young and Middle People of Shenyang,No.RC170446.
文摘Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted considerable attention for its combined effect.VSL#3 is the only probiotic considered as a kind of medical food;it mainly participates in the regulation of the intestinal barrier function,including improving tight junction protein function,balancing intestinal microbial composition,regulating immune-related cytokine expression and so on.The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans(including children).We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies,including digestive systemic diseases(gastrointestinal diseases and hepatic diseases),obesity and diabetes,allergic diseases,nervous systemic diseases,atherosclerosis,bone diseases,and female reproductive systemic diseases.
