OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bla...OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.展开更多
The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis a...The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.展开更多
A new environmental friendly catalyst, HaSiWrMo6O40/PAn was prepared and identified by means of FT-IR, XRD and TG/DTA. The optimum conditions have been found, that was, mass ratio of m（PAn）： m（HaSiW6Mo6On.） was 1...A new environmental friendly catalyst, HaSiWrMo6O40/PAn was prepared and identified by means of FT-IR, XRD and TG/DTA. The optimum conditions have been found, that was, mass ratio of m（PAn）： m（HaSiW6Mo6On.） was 1：1.25, volume of methanol was 20 mL, and the reflux reaction time was 2h. The structural identity of Keggin units was preserved after the incorporation into polyaniline matrix. H4SiW6Mo6040/PAn was used as catalyst in catalytic synthesis of acetals and ketals. Effects of n（aldehyde（ketone ））： n（glycol）, catalyst dosage and reaction time on yield were investingated. Optimal conditions were： n（aldehyde（ketone））： n（glycol）=1.0： 1.5; mass fraction of catalyst to reactants, 0.5%; reaction time, 1.0 h and cyclohexane as water-stripped reagent, 15 mL. Under these conditions, yields of actels and ketals were 31.9%-91.6%.展开更多
Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed t...Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.展开更多
Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized an...Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized and afforded excellent catalytic performance with 99.0%conversion and 97.7%selectivity to CPO in a near-neutral solution under 2.0 MPa H2 at 160℃ for 5 h,much higher than those on other molecular sieve supports including MCM-41,SBA-15,HY,and ZSM-5.A small amount of Al highly dispersed in MCM-41 plays an anchoring role and ensures the formation of highly dispersed CuNi bimetallic nanoparticles(NPs).The remarkably improved catalytic performance may be attributed to the bimetallic synergistic and charge transfer effects.In addition,the initial FA concentration and the aqueous system pH required precise control to minimize polymerization and achieve high selectivity of CPO.Fourier transform infrared spectroscopy and mass spectra results indicated that polymerization was sensitive to pH values.Under acidic conditions,FA and intermediate furfuryl alcohol polymerize,while the intermediate 4-hydroxy-2-cyclopentenone mainly polymerizes under alkaline conditions,blocking the cascade of multiple reactions.Therefore,near-neutral conditions are most suitable for minimizing the impact of polymerization.This study provides a useful solution for the current universal problems of polymerization side reactions and low carbon balance for biomass conversion.展开更多
A new environmental friendly catalyst, H3PW6Mo6O40/TiO2 was prepared. The optimum conditions have been found, that is, mass ratio of m （TiO2）： m （H3PW6Mo6O40） is 1：2.0, volume of water is 30 mL, the reflux react...A new environmental friendly catalyst, H3PW6Mo6O40/TiO2 was prepared. The optimum conditions have been found, that is, mass ratio of m （TiO2）： m （H3PW6Mo6O40） is 1：2.0, volume of water is 30 mL, the reflux reaction time is 2 h, and activated temperature is 150 ℃. H3PW6Mo6O40/TiO2 was used as catalyst in catalytic synthesis ofacetals and ketals. Effects ofn （aldehyde（ketone））： n （glycol）, catalyst dosage and reaction time on yield were investigated. Optimal conditions were： n（aldehyde （ketone））： n （glycol）=1.0 ： 1.4; mass fraction of catalyst to reactants, 0.8%; reaction time, 1.0 h and cyclohexane as water-stripped reagent, 10 mL. Under these conditions, yields of acetals and ketals can reach 53.0% -86.9 0%展开更多
Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechan...Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILl was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-[31, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Results Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Conclusions Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.展开更多
文摘OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.
基金Supported by National Institutes of Health Grant 2R01 DK080236 06A1
文摘The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.
文摘A new environmental friendly catalyst, HaSiWrMo6O40/PAn was prepared and identified by means of FT-IR, XRD and TG/DTA. The optimum conditions have been found, that was, mass ratio of m（PAn）： m（HaSiW6Mo6On.） was 1：1.25, volume of methanol was 20 mL, and the reflux reaction time was 2h. The structural identity of Keggin units was preserved after the incorporation into polyaniline matrix. H4SiW6Mo6040/PAn was used as catalyst in catalytic synthesis of acetals and ketals. Effects of n（aldehyde（ketone ））： n（glycol）, catalyst dosage and reaction time on yield were investingated. Optimal conditions were： n（aldehyde（ketone））： n（glycol）=1.0： 1.5; mass fraction of catalyst to reactants, 0.5%; reaction time, 1.0 h and cyclohexane as water-stripped reagent, 15 mL. Under these conditions, yields of actels and ketals were 31.9%-91.6%.
文摘Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.
文摘Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized and afforded excellent catalytic performance with 99.0%conversion and 97.7%selectivity to CPO in a near-neutral solution under 2.0 MPa H2 at 160℃ for 5 h,much higher than those on other molecular sieve supports including MCM-41,SBA-15,HY,and ZSM-5.A small amount of Al highly dispersed in MCM-41 plays an anchoring role and ensures the formation of highly dispersed CuNi bimetallic nanoparticles(NPs).The remarkably improved catalytic performance may be attributed to the bimetallic synergistic and charge transfer effects.In addition,the initial FA concentration and the aqueous system pH required precise control to minimize polymerization and achieve high selectivity of CPO.Fourier transform infrared spectroscopy and mass spectra results indicated that polymerization was sensitive to pH values.Under acidic conditions,FA and intermediate furfuryl alcohol polymerize,while the intermediate 4-hydroxy-2-cyclopentenone mainly polymerizes under alkaline conditions,blocking the cascade of multiple reactions.Therefore,near-neutral conditions are most suitable for minimizing the impact of polymerization.This study provides a useful solution for the current universal problems of polymerization side reactions and low carbon balance for biomass conversion.
基金Acknowledgements： This work was financially supported by the Natural Science Foundation of Hubei Province, China （No. 2005ABA053） and the National Natural Science Foundation of China （No. 20471044）.
文摘A new environmental friendly catalyst, H3PW6Mo6O40/TiO2 was prepared. The optimum conditions have been found, that is, mass ratio of m （TiO2）： m （H3PW6Mo6O40） is 1：2.0, volume of water is 30 mL, the reflux reaction time is 2 h, and activated temperature is 150 ℃. H3PW6Mo6O40/TiO2 was used as catalyst in catalytic synthesis ofacetals and ketals. Effects ofn （aldehyde（ketone））： n （glycol）, catalyst dosage and reaction time on yield were investigated. Optimal conditions were： n（aldehyde （ketone））： n （glycol）=1.0 ： 1.4; mass fraction of catalyst to reactants, 0.8%; reaction time, 1.0 h and cyclohexane as water-stripped reagent, 10 mL. Under these conditions, yields of acetals and ketals can reach 53.0% -86.9 0%
基金supported by grants from the National Natural Science Foundation of China(No.30900384)Education Bureau Foundation of Liaoning Province,China (No.2009a723)
文摘Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILl was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-[31, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Results Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Conclusions Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.
