Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety o...Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.展开更多
Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life st...Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life style might inhibit prostate cancer progression. Cancer chemoprevention has emerged as an important factor in controlling cancer development through natural or synthetic compounds. Oxidative stress is among the factors contributing to prostate cancer development. The transcription factor nuclear factor(erythroid-derived 2)-like 2(Nrf2) controls detoxifying antioxidant enzymes expression by binding to the antioxidant response element(ARE) in the promoter of these genes to activate their expression. Many natural products can fight oxidative stress and protects cells from DNA damage by activating the Nrf2/ARE pathway. High consumption of fruits and vegetables can reduce disease incidence and invasive tumors. In this review, the roles of important fruit and vegetable phytochemicals in regulating prostate cancer progression and tumor growth are discussed.展开更多
The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome libr...The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome library screening,we evaluated Kelch-like ECH-associated protein 1(KEAP1)as a key regulator of sorafenib’s susceptibility in HCC.We also investigated whether KEAP1’s knockdown can stabilize nuclear factor(erythroid-derived 2)-like 2(NRF2)protein levels that led to sorafenib’s resistance,including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC’s growth in vitro and in vivo.Furthermore,we clarified that fibroblast growth factor 21(FGF21)is an important downstream regulator of NRF2 in HCC.Intriguingly,we observed that FGF21 bound to NRF2 through the C-terminus of FGF21,thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC.These findings,therefore,propose that targeting FGF21 is a promising strategy to combat HCC sorafenib’s resistance.展开更多
The potential of a phytogenic premix(PP)based on ginger,lemon balm,oregano and thyme to stimulate the expression of cytoprotective genes at the broiler gut level was evaluated in this study.In particular,the effects o...The potential of a phytogenic premix(PP)based on ginger,lemon balm,oregano and thyme to stimulate the expression of cytoprotective genes at the broiler gut level was evaluated in this study.In particular,the effects of PP inclusion levels on a selection of genes related to host protection against oxidation(catalase[GAT],superoxide dismutase 1[SOD1],glutathione peroxidase 2[GPX2],heme oxygenase 1[HMOX1],NAD(P)H quinone dehydrogenase 1[NQO1],nuclear factor(erythroid-derived 2)-like 2[Nrf2]and kelch like ECH associated protein 1[Keap1]),stress(heat shock 70 kDa protein 2[HSP70]and heat shock protein 90 alpha family class A member 1[HSP90])and inflammation(nuclear factor kappa B subunit 1[NF-κB1],Toll-like receptor 2 family member B(TLR2 B)and Toll-like receptor 4[TLR4])were profiled along the broiler intestine.In addition,broiler intestinal segments were assayed for their total antioxidant capacity(TAC).Depending on PP inclusion level(i.e.0,750,1,000 and 2,000 mg/kg diet)in the basal diets,1-d-old Cobb broiler chickens(n=500)were assigned into the following 4 treatments:CON,PP-750,PP-1000 and PP-2000.Each treatment had 5 replicates of 25 chickens with ad libitum access to feed and water.Data were analyzed by ANOVA and means compared using Tukey’s honest significant difference(HSD)test.Polynomial contrasts tested the linear and quadratic effect of PP inclusion levels.Inclusion of PP increased(P≤0.05)the expression of cytoprotective genes against oxidation,except CAT.In particular,the cytoprotective against oxidation genes were up-regulated primarily in the duodenum and the ceca and secondarily in the jejunum.Most of the genes were upregulated in a quadratic manner with increasing PP inclusion level with the highest expression levels noted in treatments PP-750 and PP-1000 compared to CON.Similarly,intestinal TAC was higher in PP-1000 in the duodenum(P=0.011)and the ceca(P=0.050)compared to CON.Finally,increasing PP inclusion level resulted in linearly reduced(P<0.05)expression of NF-κB1,TLR4 and HSP70,the former展开更多
基金Supported by An operating grant from Canadian Institutes of Health Research,No.89887 to Jin TRa NSFC grant,No.81072300 to Jin TR and Yu ZWa NSFC grant,No.30730079 to Ling WH in part
文摘Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.
基金supported in part by Institutional Funds and from the National Cancer Institute(Grant No.R01-CA118947,R01-CA152826)the National Center for Complementary and Alt ernative Medicines and the Office of Dietary Supplements(Grant No.R01AT007065)
文摘Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life style might inhibit prostate cancer progression. Cancer chemoprevention has emerged as an important factor in controlling cancer development through natural or synthetic compounds. Oxidative stress is among the factors contributing to prostate cancer development. The transcription factor nuclear factor(erythroid-derived 2)-like 2(Nrf2) controls detoxifying antioxidant enzymes expression by binding to the antioxidant response element(ARE) in the promoter of these genes to activate their expression. Many natural products can fight oxidative stress and protects cells from DNA damage by activating the Nrf2/ARE pathway. High consumption of fruits and vegetables can reduce disease incidence and invasive tumors. In this review, the roles of important fruit and vegetable phytochemicals in regulating prostate cancer progression and tumor growth are discussed.
基金supported by the National Natural Science Foundation of China(81702981,81827804,81902367,81772546and LQ18H160010)Zhejiang Provincial Natural Science Foundation of China(LY20H160021 and Y15H160052)+1 种基金China Postdoctoral Science Foundation(2020T130584 and 2020M671755)Health Innovation Talent Support Project of Zhejiang Medical and Health Science and Technology Plan(2021447581)。
文摘The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome library screening,we evaluated Kelch-like ECH-associated protein 1(KEAP1)as a key regulator of sorafenib’s susceptibility in HCC.We also investigated whether KEAP1’s knockdown can stabilize nuclear factor(erythroid-derived 2)-like 2(NRF2)protein levels that led to sorafenib’s resistance,including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC’s growth in vitro and in vivo.Furthermore,we clarified that fibroblast growth factor 21(FGF21)is an important downstream regulator of NRF2 in HCC.Intriguingly,we observed that FGF21 bound to NRF2 through the C-terminus of FGF21,thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC.These findings,therefore,propose that targeting FGF21 is a promising strategy to combat HCC sorafenib’s resistance.
基金ANCO Animal Nutrition Competence GmbH for provision of the PP and research funding(AUA research agreement 06.0068)
文摘The potential of a phytogenic premix(PP)based on ginger,lemon balm,oregano and thyme to stimulate the expression of cytoprotective genes at the broiler gut level was evaluated in this study.In particular,the effects of PP inclusion levels on a selection of genes related to host protection against oxidation(catalase[GAT],superoxide dismutase 1[SOD1],glutathione peroxidase 2[GPX2],heme oxygenase 1[HMOX1],NAD(P)H quinone dehydrogenase 1[NQO1],nuclear factor(erythroid-derived 2)-like 2[Nrf2]and kelch like ECH associated protein 1[Keap1]),stress(heat shock 70 kDa protein 2[HSP70]and heat shock protein 90 alpha family class A member 1[HSP90])and inflammation(nuclear factor kappa B subunit 1[NF-κB1],Toll-like receptor 2 family member B(TLR2 B)and Toll-like receptor 4[TLR4])were profiled along the broiler intestine.In addition,broiler intestinal segments were assayed for their total antioxidant capacity(TAC).Depending on PP inclusion level(i.e.0,750,1,000 and 2,000 mg/kg diet)in the basal diets,1-d-old Cobb broiler chickens(n=500)were assigned into the following 4 treatments:CON,PP-750,PP-1000 and PP-2000.Each treatment had 5 replicates of 25 chickens with ad libitum access to feed and water.Data were analyzed by ANOVA and means compared using Tukey’s honest significant difference(HSD)test.Polynomial contrasts tested the linear and quadratic effect of PP inclusion levels.Inclusion of PP increased(P≤0.05)the expression of cytoprotective genes against oxidation,except CAT.In particular,the cytoprotective against oxidation genes were up-regulated primarily in the duodenum and the ceca and secondarily in the jejunum.Most of the genes were upregulated in a quadratic manner with increasing PP inclusion level with the highest expression levels noted in treatments PP-750 and PP-1000 compared to CON.Similarly,intestinal TAC was higher in PP-1000 in the duodenum(P=0.011)and the ceca(P=0.050)compared to CON.Finally,increasing PP inclusion level resulted in linearly reduced(P<0.05)expression of NF-κB1,TLR4 and HSP70,the former
