AIM:To investigate the effects of blueberry on hepatic fibrosis and NF-E2-related factor 2(Nrf2) transcription factor in rats.METHODS:Forty-five male Sprague-Dawley rats were randomly divided into control group(A);CCl...AIM:To investigate the effects of blueberry on hepatic fibrosis and NF-E2-related factor 2(Nrf2) transcription factor in rats.METHODS:Forty-five male Sprague-Dawley rats were randomly divided into control group(A);CCl4-induced hepatic fibrosis group(B);blueberry prevention group(C);Dan-shao-hua-xian capsule(DSHX) prevention group(D);and blueberry + DSHX prevention group(E).Liver fibrosis was induced in rats by subcutaneous injection of CCl4 and a high-lipid/low-protein diet for 8 wk(except the control group).The level of hyaluronic acid(HA) and alanine aminotransferase(ALT) in serum was examined.The activity of superoxide dismutase(SOD),glutathione-S-transferase(GST) and malondialdehyde(MDA) in liver homogenates was determined.The degree of hepatic fibrosis was evaluated by hematoxylin and eosin and Masson staining.Expression of Nrf2 and NADPH quinone oxidoreductase 1(Nqo1) was detected by real-time reversed transcribed-polymerase chain reaction,immunohistochemical techniques,and western blotting.RESULTS:Compared with group B,liver indices,levels of serum HA and ALT of groups C,D and E were reduced(liver indices:0.038 ± 0.008,0.036 ± 0.007,0.036 ± 0.005 vs 0.054 ± 0.009,P<0.05;HA:502.33 ± 110.57 ng/mL,524.25 ± 255.42 ng/mL,499.25 ± 198.10 ng/mL vs 828.50 ± 237.83 ng/mL,P<0.05;ALT:149.44 ± 16.51 U/L,136.88 ± 10.07 U/L,127.38 ± 11.03 U/L vs 203.25 ± 31.62 U/L,P<0.05),and SOD level was significantly higher,but MDA level was lower,in liver homogenates(SOD:1.36 ± 0.09 U/mg,1.42 ± 0.13 U/mg,1.50 ± 0.15 U/mg vs 1.08 ± 0.19 U/mg,P<0.05;MDA:0.294 ± 0.026 nmol/mg,0.285 ± 0.025 nmol/mg,0.284 ± 0.028 nmol/mg vs 0.335 ± 0.056 nmol/mg,P<0.05).Meanwhile,the stage of hepatic fibrosis was significantly weakened(P<0.05).Compared with group A,the activity of GST liver homogenates and expression levels of Nrf2 and Nqo1 in group B were elevated(P<0.05).The expression level of Nrf2 and Nqo1 in groups C,D,and E were increased as compared with group B,but the difference was not significant.CONCLUSION:Blueberry has pr展开更多
Background: Pyrroloquinoline quinone(PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of t...Background: Pyrroloquinoline quinone(PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium(PQQ·Na2) on reproductive performance in sows.Results: Dietary supplementation with PQQ·Na2 significantly increased the total number of piglets born, the number of piglets born alive and the born alive litter weight. It also increased the antioxidant status in the placenta, plasma and milk. The concentration of NO was significantly increased in the plasma and placenta. RNA-seq analysis showed that462 unigenes were differentially expressed between the control(Con) treatment and PQQ treatment groups.Among these unigenes, 199 were upregulated, while 263 unigenes were downregulated. The assigned functions of the unigenes covered a broad range of GO categories. Reproduction(27, 7.03%) and the reproduction process(27, 7.03%) were assigned to the biological process category. By matching DEGs to the KEGG database, we identified 29 pathways.Conclusions: In conclusion, dietary supplementation with PQQ·Na2 in gestating and lactating sows had positive effects on their reproductive performance.展开更多
Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metab...Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.展开更多
Redox flow batteries(RFBs)are promising candidates to establish a grid-scale energy storage system for intermittent energy sources.While the current technology of vanadium RFBs has been widely exploited across the wor...Redox flow batteries(RFBs)are promising candidates to establish a grid-scale energy storage system for intermittent energy sources.While the current technology of vanadium RFBs has been widely exploited across the world,the rise in the price of vanadium and its limited volumetric energy density have necessitated the development of new kinds of redox active molecules.Organic molecules can be used as new and economical redox couples in RFBs to address these issues.In addition,the redox organic species also provide ample advantages to increase the voltage and solubility,provide multiple numbers of electron transfer,and ensure electrochemical/chemical stability by molecular engineering through simple synthetic methods.This review focuses on the recent developments in aqueous organic RFBs,including the molecular design and the corresponding cycling performance as these organic redox molecules are employed as either the negolyte or posolyte.Various strategies for tuning the electrochemical/chemical characteristics of organic molecules have improved their solubility,redox potential cycling stability,and crossover issue across a separating membrane.We also put forward new strategies using nanotechnology and our perspective for the future development of this rapidly growing field.展开更多
It was found that at neutral pH the hydroxylation reaction rate of phenol was accelerated with an increase of the amounts of 1,4 quinone (1,4 BQ). This acceleration was ascribed to the formation of semiquinone from 1,...It was found that at neutral pH the hydroxylation reaction rate of phenol was accelerated with an increase of the amounts of 1,4 quinone (1,4 BQ). This acceleration was ascribed to the formation of semiquinone from 1,4 BQ. The semiquinone and 1,4 BQ were suggested to play a role of actual oxidant (electron transfer) in the catalytic cycle. With further reaction, most 1,4 BQ was converted into 1,4 hydroquinone (HQ) and the corresponding mechanism was proposed.展开更多
In this work,we demonstrated that the quinone structure can quench the fluorescence of the carbon dots(CDs).The sensitive determination of dopamine(DA) was studied primarily based on this principle.DA would be transfo...In this work,we demonstrated that the quinone structure can quench the fluorescence of the carbon dots(CDs).The sensitive determination of dopamine(DA) was studied primarily based on this principle.DA would be transformed into DA quinone under alkaline conditions,which resulted in fluorescence quenching of the CDs.A good linear range from 5 nmol/L to 0.4 mmol/L was obtained and the detection limit was 1 nmol/L.Moreover,the quenching effect of quinone structure on the fluorescence of CDs was confirmed by Fourier transform infrared spectra,time-correlated single-photon counting and X-ray photoelectron spectroscopy.Remarkably,CDs were firstly applied to detect the quinone drugs quantitatively which contained typical quinone structure based on the quenching mechanism.More than this,the sensing platform was demonstrated to provide credible selectivity and satisfactory stability in human serum solution with good liner range.Hence,our practical application and mechanism have showed great potential for diagnostic purposes.展开更多
Pyrroloquinoline quinone （PQQ） plays a sig- nificant role as a redox cofactor in combination with dehydrogenases in bacteria. These dehydrogenases play key roles in the oxidation of important substrates for the biot...Pyrroloquinoline quinone （PQQ） plays a sig- nificant role as a redox cofactor in combination with dehydrogenases in bacteria. These dehydrogenases play key roles in the oxidation of important substrates for the biotechnology industry, such as vitamin C production. While biosynthesis of PQQ genes has been widely studied, PQQ-transport mechanisms used both two-dimensional remain unclear. Herein, we fluorescence-difference gel electrophoresis tandem mass spectrometry and RNA sequencing to investigate the effects ofpqqB overexpres- sion in an industrial strain of Gluconobacter oxydans WSH-003. We have identified 73 differentially expressed proteins and 99 differentially expressed genes, a majority of which are related to oxidation-reduction and transport processes by gene ontology analysis. We also described several putative candidate effectors that responded to increased PQQ levels resulting from pqqB overexpression. Furthermore, quantitative PCR was used to verify five putative PQQ-transport genes among different PQQ producing strains, and the results showed that ompW, B932 1930 and B932_2186 were upregulated in all conditions. Then the three genes were over-expressed in G. oxydans WSH-003 and PQQ production were detected. The results showed that extracellular PQQ of B932_1930 （a transporter） and B932_2186 （an ABC transporter perrnease） overexpression strains were enhanced by 1.77- fold and 1.67-fold, respectively. The results suggest that the proteins encoded by PqqB, B932_1930 and B932 2186 might enhance the PQQ secretion process.展开更多
Acidithiobacillus caldus,a typical sulfur oxidizer,derives the majority of its energy from sulfur oxidation.And the essential enzyme for sulfide oxidation catalysis is sulfide quinone oxidoreductase(SQR),an ancient fl...Acidithiobacillus caldus,a typical sulfur oxidizer,derives the majority of its energy from sulfur oxidation.And the essential enzyme for sulfide oxidation catalysis is sulfide quinone oxidoreductase(SQR),an ancient flavoprotein.Here,the catalytic mechanism of SQR generated from A.caldus was investigated(SQR^(Ac)).According to phylogenetic study,SQR^(Ac)(ACAty RS11315)is closely related to SQR(BAD99305)of Acidithiobacillus ferrooxidans NASF-1 and is classified as a type I Sqr enzyme.SQR^(Ac)heterologously produced in Escherichia coli exhibits the distinctive absorption peaks(375,450 nm)of the flavoproteins family of proteins in its absorption spectrum.Utilizing site-directed mutagenesis,the function of conserved cysteines in the catalytic pathway was determined.Based on the sulfide quinone redox reactions in vitro of SQR^(Ac)and variations,Cys160 and Cys356 have been identified as enzyme-active residues.Mutation of another cysteine present in all type I SQRs(Cys128)decreased enzyme activity by 56%,indicating that this residue plays an important but non-essential role in enzyme function.In addition,the binding affinities of SQR^(Ac),the visualization of its 3D structure,and the interaction between receptors and ligands were investigated.Finally,a suitable sulfide quinone redox catalytic mechanism for A.caldus was proposed.展开更多
Background:Oxidative stress is a main cause of piglet gut damage and diarrhea.Pyrroloquinoline quinone(PQQ),is a novel redox cofactor with antioxidant properties.However,the effect and mechanism that PQQ supplementati...Background:Oxidative stress is a main cause of piglet gut damage and diarrhea.Pyrroloquinoline quinone(PQQ),is a novel redox cofactor with antioxidant properties.However,the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood.Therefore,the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line(IPEC-J2)challenged with H_(2)O_(2).Results:Experiment 1,144 Duroc×Landrace×Yorkshire pigs(weaned at 28 d)were allocated to four groups:received a basal diet(control)and diets supplemented with 0.15%,0.30%and 0.45%PQQ,respectively.On d 28,growth performance,diarrhea incidence and redox factors were measured.Experiment 2,IPEC-J2 were treated with or without PQQ in the presence or absence of H_(2)O_(2)for indicated time points.Experiment 3,IPEC-J2 were transfected with or without Nrf2 siRNA,then treated according to Experiment 2.The cell viability,redox factors,protein of tight junctions and Nrf2 pathway were determined.In vivo,PQQ supplementation demonstrated dose-related improvements in average daily gain,and gain to feed ratio(Linear P<0.05).During d 0–28,compared to controls,0.45%PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum,and increased concentration of SOD in liver;0.3%PQQ supplementation decreased ileal and liver MDA concentration;and 0.15%PQQ supplementation decreased ileal MDA concentration(P<0.05).In vitro,compared to cells cultured with H_(2)O_(2),pre-treatment with PQQ increased cell viability,tight junction proteins expression including ZO-1,ZO-2,Occludin and Claudin-1;and decreased ROS concentration and level of Caspase-3(P<0.05);as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2,HO-1.Notably,Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H_(2)O_(2)-induced intracellular changes.Conclusion展开更多
Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly straine...Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.展开更多
基金Supported by A grant from Foundation of High Level Talented Specialists of Guizhou Province,China,No. TZJF-200850a grant from Foundation of the Program for Tackling Key Problems of Guizhou Science and Technology Department,China,No. 2010GZ97666
文摘AIM:To investigate the effects of blueberry on hepatic fibrosis and NF-E2-related factor 2(Nrf2) transcription factor in rats.METHODS:Forty-five male Sprague-Dawley rats were randomly divided into control group(A);CCl4-induced hepatic fibrosis group(B);blueberry prevention group(C);Dan-shao-hua-xian capsule(DSHX) prevention group(D);and blueberry + DSHX prevention group(E).Liver fibrosis was induced in rats by subcutaneous injection of CCl4 and a high-lipid/low-protein diet for 8 wk(except the control group).The level of hyaluronic acid(HA) and alanine aminotransferase(ALT) in serum was examined.The activity of superoxide dismutase(SOD),glutathione-S-transferase(GST) and malondialdehyde(MDA) in liver homogenates was determined.The degree of hepatic fibrosis was evaluated by hematoxylin and eosin and Masson staining.Expression of Nrf2 and NADPH quinone oxidoreductase 1(Nqo1) was detected by real-time reversed transcribed-polymerase chain reaction,immunohistochemical techniques,and western blotting.RESULTS:Compared with group B,liver indices,levels of serum HA and ALT of groups C,D and E were reduced(liver indices:0.038 ± 0.008,0.036 ± 0.007,0.036 ± 0.005 vs 0.054 ± 0.009,P<0.05;HA:502.33 ± 110.57 ng/mL,524.25 ± 255.42 ng/mL,499.25 ± 198.10 ng/mL vs 828.50 ± 237.83 ng/mL,P<0.05;ALT:149.44 ± 16.51 U/L,136.88 ± 10.07 U/L,127.38 ± 11.03 U/L vs 203.25 ± 31.62 U/L,P<0.05),and SOD level was significantly higher,but MDA level was lower,in liver homogenates(SOD:1.36 ± 0.09 U/mg,1.42 ± 0.13 U/mg,1.50 ± 0.15 U/mg vs 1.08 ± 0.19 U/mg,P<0.05;MDA:0.294 ± 0.026 nmol/mg,0.285 ± 0.025 nmol/mg,0.284 ± 0.028 nmol/mg vs 0.335 ± 0.056 nmol/mg,P<0.05).Meanwhile,the stage of hepatic fibrosis was significantly weakened(P<0.05).Compared with group A,the activity of GST liver homogenates and expression levels of Nrf2 and Nqo1 in group B were elevated(P<0.05).The expression level of Nrf2 and Nqo1 in groups C,D,and E were increased as compared with group B,but the difference was not significant.CONCLUSION:Blueberry has pr
基金supported by the National Key Research and Development Plan of China(2016YFD0501207)the China Agriculture Research System(CARS-36)
文摘Background: Pyrroloquinoline quinone(PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium(PQQ·Na2) on reproductive performance in sows.Results: Dietary supplementation with PQQ·Na2 significantly increased the total number of piglets born, the number of piglets born alive and the born alive litter weight. It also increased the antioxidant status in the placenta, plasma and milk. The concentration of NO was significantly increased in the plasma and placenta. RNA-seq analysis showed that462 unigenes were differentially expressed between the control(Con) treatment and PQQ treatment groups.Among these unigenes, 199 were upregulated, while 263 unigenes were downregulated. The assigned functions of the unigenes covered a broad range of GO categories. Reproduction(27, 7.03%) and the reproduction process(27, 7.03%) were assigned to the biological process category. By matching DEGs to the KEGG database, we identified 29 pathways.Conclusions: In conclusion, dietary supplementation with PQQ·Na2 in gestating and lactating sows had positive effects on their reproductive performance.
文摘Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.
文摘Redox flow batteries(RFBs)are promising candidates to establish a grid-scale energy storage system for intermittent energy sources.While the current technology of vanadium RFBs has been widely exploited across the world,the rise in the price of vanadium and its limited volumetric energy density have necessitated the development of new kinds of redox active molecules.Organic molecules can be used as new and economical redox couples in RFBs to address these issues.In addition,the redox organic species also provide ample advantages to increase the voltage and solubility,provide multiple numbers of electron transfer,and ensure electrochemical/chemical stability by molecular engineering through simple synthetic methods.This review focuses on the recent developments in aqueous organic RFBs,including the molecular design and the corresponding cycling performance as these organic redox molecules are employed as either the negolyte or posolyte.Various strategies for tuning the electrochemical/chemical characteristics of organic molecules have improved their solubility,redox potential cycling stability,and crossover issue across a separating membrane.We also put forward new strategies using nanotechnology and our perspective for the future development of this rapidly growing field.
文摘It was found that at neutral pH the hydroxylation reaction rate of phenol was accelerated with an increase of the amounts of 1,4 quinone (1,4 BQ). This acceleration was ascribed to the formation of semiquinone from 1,4 BQ. The semiquinone and 1,4 BQ were suggested to play a role of actual oxidant (electron transfer) in the catalytic cycle. With further reaction, most 1,4 BQ was converted into 1,4 hydroquinone (HQ) and the corresponding mechanism was proposed.
基金supported by the National Natural Science Foundation of China (61178035,61571426,61671435,81671845,81630053,51428301,and 31572343)the National High Technology R&D Program of China (2015BAI23H01)Beijing Natural Science Foundation (4161003)
文摘In this work,we demonstrated that the quinone structure can quench the fluorescence of the carbon dots(CDs).The sensitive determination of dopamine(DA) was studied primarily based on this principle.DA would be transformed into DA quinone under alkaline conditions,which resulted in fluorescence quenching of the CDs.A good linear range from 5 nmol/L to 0.4 mmol/L was obtained and the detection limit was 1 nmol/L.Moreover,the quenching effect of quinone structure on the fluorescence of CDs was confirmed by Fourier transform infrared spectra,time-correlated single-photon counting and X-ray photoelectron spectroscopy.Remarkably,CDs were firstly applied to detect the quinone drugs quantitatively which contained typical quinone structure based on the quenching mechanism.More than this,the sensing platform was demonstrated to provide credible selectivity and satisfactory stability in human serum solution with good liner range.Hence,our practical application and mechanism have showed great potential for diagnostic purposes.
基金This work was supported by grants from the National High Technology Research and Development Program of China （863 Program, 2012AA022103）, the National Basic Research Program of China （973 Program, 2013CB733602, 2014CB745100）, the Major Program of National Natural Science Foundation of China （Grant No. 21390204）, the Program for New Century Excellent Talents in University （NCET-12-0876）, the Foundation for the Author of National Excellent Doctoral Dissertation of China （FANEDD, 201256）, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the 111 Project （111-2-06）.
文摘Pyrroloquinoline quinone （PQQ） plays a sig- nificant role as a redox cofactor in combination with dehydrogenases in bacteria. These dehydrogenases play key roles in the oxidation of important substrates for the biotechnology industry, such as vitamin C production. While biosynthesis of PQQ genes has been widely studied, PQQ-transport mechanisms used both two-dimensional remain unclear. Herein, we fluorescence-difference gel electrophoresis tandem mass spectrometry and RNA sequencing to investigate the effects ofpqqB overexpres- sion in an industrial strain of Gluconobacter oxydans WSH-003. We have identified 73 differentially expressed proteins and 99 differentially expressed genes, a majority of which are related to oxidation-reduction and transport processes by gene ontology analysis. We also described several putative candidate effectors that responded to increased PQQ levels resulting from pqqB overexpression. Furthermore, quantitative PCR was used to verify five putative PQQ-transport genes among different PQQ producing strains, and the results showed that ompW, B932 1930 and B932_2186 were upregulated in all conditions. Then the three genes were over-expressed in G. oxydans WSH-003 and PQQ production were detected. The results showed that extracellular PQQ of B932_1930 （a transporter） and B932_2186 （an ABC transporter perrnease） overexpression strains were enhanced by 1.77- fold and 1.67-fold, respectively. The results suggest that the proteins encoded by PqqB, B932_1930 and B932 2186 might enhance the PQQ secretion process.
基金the National Key Research and Development Program of China(2022YFC3401300)the National Natural Science Foundation of China(No.21878128,21,776,113,31,701,582+2 种基金21,606,110)the Fundamental Research Funds for the Central Universities(No.2050205)Program of Introducing Talents of Discipline to Universities(No.111-2-06).
文摘Acidithiobacillus caldus,a typical sulfur oxidizer,derives the majority of its energy from sulfur oxidation.And the essential enzyme for sulfide oxidation catalysis is sulfide quinone oxidoreductase(SQR),an ancient flavoprotein.Here,the catalytic mechanism of SQR generated from A.caldus was investigated(SQR^(Ac)).According to phylogenetic study,SQR^(Ac)(ACAty RS11315)is closely related to SQR(BAD99305)of Acidithiobacillus ferrooxidans NASF-1 and is classified as a type I Sqr enzyme.SQR^(Ac)heterologously produced in Escherichia coli exhibits the distinctive absorption peaks(375,450 nm)of the flavoproteins family of proteins in its absorption spectrum.Utilizing site-directed mutagenesis,the function of conserved cysteines in the catalytic pathway was determined.Based on the sulfide quinone redox reactions in vitro of SQR^(Ac)and variations,Cys160 and Cys356 have been identified as enzyme-active residues.Mutation of another cysteine present in all type I SQRs(Cys128)decreased enzyme activity by 56%,indicating that this residue plays an important but non-essential role in enzyme function.In addition,the binding affinities of SQR^(Ac),the visualization of its 3D structure,and the interaction between receptors and ligands were investigated.Finally,a suitable sulfide quinone redox catalytic mechanism for A.caldus was proposed.
基金supported by the National Natural Science Foundation of China(Grant No.32072772,31672459,31372317 and 30871808).
文摘Background:Oxidative stress is a main cause of piglet gut damage and diarrhea.Pyrroloquinoline quinone(PQQ),is a novel redox cofactor with antioxidant properties.However,the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood.Therefore,the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line(IPEC-J2)challenged with H_(2)O_(2).Results:Experiment 1,144 Duroc×Landrace×Yorkshire pigs(weaned at 28 d)were allocated to four groups:received a basal diet(control)and diets supplemented with 0.15%,0.30%and 0.45%PQQ,respectively.On d 28,growth performance,diarrhea incidence and redox factors were measured.Experiment 2,IPEC-J2 were treated with or without PQQ in the presence or absence of H_(2)O_(2)for indicated time points.Experiment 3,IPEC-J2 were transfected with or without Nrf2 siRNA,then treated according to Experiment 2.The cell viability,redox factors,protein of tight junctions and Nrf2 pathway were determined.In vivo,PQQ supplementation demonstrated dose-related improvements in average daily gain,and gain to feed ratio(Linear P<0.05).During d 0–28,compared to controls,0.45%PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum,and increased concentration of SOD in liver;0.3%PQQ supplementation decreased ileal and liver MDA concentration;and 0.15%PQQ supplementation decreased ileal MDA concentration(P<0.05).In vitro,compared to cells cultured with H_(2)O_(2),pre-treatment with PQQ increased cell viability,tight junction proteins expression including ZO-1,ZO-2,Occludin and Claudin-1;and decreased ROS concentration and level of Caspase-3(P<0.05);as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2,HO-1.Notably,Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H_(2)O_(2)-induced intracellular changes.Conclusion
基金financially supported by the National Natural Science Foundation of China(Nos.22171146,21971121,and 22188101 to ZL)the China Postdoctoral Science Foundation(No.2021M701775 to CC)。
文摘Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.
