The polyphagous B-biotype of Bemisia tabaci (Gennadius) has demonstrated a high capacity to adapt to numerous hosts from diverse plant families. To illustrate induced responses by the host plant, biochemical researc...The polyphagous B-biotype of Bemisia tabaci (Gennadius) has demonstrated a high capacity to adapt to numerous hosts from diverse plant families. To illustrate induced responses by the host plant, biochemical research on eight plant-insect interaction correlative enzymes, representing detoxifying, antioxidant and digestive pathways, were investigated. Transferring whitefly adults to Zhongmian 23 from the pre-adapted host Zhongmian 41 induced activities of carboxylesterase (by 1.80-fold), glutathione S-transferase (by 3.79-fold), proteinase (by 1.62-fold) and amylase (by 2.41-fold) activities, hut decreased polyphenol oxidase (by 1.89-fold) and peroxidase (by 1.88-fold). However, transferring whitefly adults to the favorite host abutilon from Zhongmian 41 was associated with increased activities of cytochrome P450 monooxygenase (by 1.61-fold) and amylase (by 1.42-fold), and decreased activities of polyphenol oxidase (by 2.96-fold) and peroxidase (by 2.07-fold). Our results, together with previous studies, proved that multiple pathways are involved in coping with host shifts by polyphagous herbivores, and the taxonomic status and preference of the host transferred would affect which pathway would be induced. These results would represent a key challenge in developing long-term sustainable insect control strategies.展开更多
BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the...BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.展开更多
BACKGROUND: 10-23 DNA enzyme is one kind of de-oxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2. 2. 15 cells were demonstrated previously. The aim ...BACKGROUND: 10-23 DNA enzyme is one kind of de-oxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2. 2. 15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A1816UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km,Kcat and Kcat/ Km for Drz-HBV-C-9, were 1.4 ×10-9 mol, 1.6 min-1 and 1.1 × 109 mol-1 · min-1, respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.展开更多
AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy...AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB.展开更多
The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a...The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.展开更多
B vitamins are enzyme cofactors that play an important role in energy metabolism.The aim of this study was to elucidate whether B vitamin administration can reduce body weight(BW)gain by improving energy metabolism-re...B vitamins are enzyme cofactors that play an important role in energy metabolism.The aim of this study was to elucidate whether B vitamin administration can reduce body weight(BW)gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet.Fifty rats were randomly assigned to one of the following five groups:control group(C),including rats fed on standard rat chow;four treatment groups(H0,H1,H2,and H3),in which rats were fed on a high-fat diet.Rats in the H1 group were treated daily with 100 mg/kg BW thiamine(VB1),100 mg/kg BW riboflavin(VB2),and 250 mg/kg BW niacin(VPP);rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine(VB6),100 mg/kg BW cobalamin(VB12),and 5 mg/kg BW folate(FA);and rats in the H3 group were treated daily with all of the B vitamins administered to the H1 and H2 groups.After 12 weeks,the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the H1 and C groups,respectively,which were significantly less than the changes in the H0 group(285.2±14.8 g,P〈0.05).In the H0 group,the plasma total cholesterol(CHO)and triglyceride(TG)levels were 1.59±0.30 mmol/L and 1.55±0.40 mmol/L,respectively,which were significantly greater than those in the H1 group(1.19±0.18 mmol/L and 0.76±0.34 mmol/L,respectively,P〈0.05).The activities of transketolase(TK),glutathione reductase,and Na^+/K^+adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the H0 group(P〈0.05).Furthermore,the glucose-6-phosphate dehydrogenase,pyruvic acid kinase,and succinate dehydrogenase activities also were increased after treatment with B vitamins.Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats,thus possibly providing potential benefits to humans.展开更多
AIM: To evaluate tumor necrosis factor-α converting enzyme(TACE) methylation status in patients with chronic hepatitis B(CHB).METHODS: Eighty patients with hepatitis B e antigen(HBe Ag)-positive CHB, 80 with HBe Ag-n...AIM: To evaluate tumor necrosis factor-α converting enzyme(TACE) methylation status in patients with chronic hepatitis B(CHB).METHODS: Eighty patients with hepatitis B e antigen(HBe Ag)-positive CHB, 80 with HBe Ag-negative CHB, and 40 healthy controls(HCs) were randomly enrolled in this study. Genomic DNA was extracted from peripheral blood mononuclear cells and methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The clinical and laboratory parameters were collected.RESULTS: One hundred and thirty of 160 patients with CHB(81.25%) and 38 of 40 HCs(95%) displayed TACE promoter methylation. The difference was significant(χ2 = 4.501, P < 0.05). TACE promoter methylation frequency in HBe Ag-positive CHB(58/80, 72.5%) was significantly lower than that in HBe Ag-negative CHB(72/80, 90%; χ2 = 8.041, P < 0.01) and HCs(χ2 = 8.438, P < 0.01). However, no significant difference was observed in the methylation frequency between HBe Agnegative CHB and HCs(χ2 = 0.873, P > 0.05). In the HBe Ag-positive group, TACE methylation frequency was significantly negatively correlated with HBe Ag(r =-0.602, P < 0.01), alanine aminotransferase(r =-0.461, P < 0.01) and aspartate aminotransferase(r =-0.329, P < 0.01). CONCLUSION: Patients with HBe Ag-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBe Ag seroconversion.展开更多
Lead (Pb) is an environmental pollutant extremely toxic to plants and other living organisms including humans. In order to research the relieve effect of Bacillus subtilis QM3 on wheat roots (Triticum aestivum L.), af...Lead (Pb) is an environmental pollutant extremely toxic to plants and other living organisms including humans. In order to research the relieve effect of Bacillus subtilis QM3 on wheat roots (Triticum aestivum L.), after wheat seeds germination for two days, wheat root caused, the experimental materials were divided into four large groups and each large group was placed in 6 petri dishes as six small groups, and then four large groups respectively cultivated with sterile water (CK), 108 CFU/ml B. subtilis QM3 (B1), 107 CFU/ml B. subtilis QM3 (B2) and 106 CFU/ml B. subtilis QM3 (B3) for 2 days, after that stressed with lead nitrate, Pb (NO)2, Pb2+ concentration calculation at five concentrations (50, 250, 500, 1000, 2000 mg/L), sterile water and different Pb2+ concentration liquid respectively cultivated the 6 small groups in each large group measuring root morpholog and assaying changes of antioxidant enzyme activity. The results showed that: with the increase of the Pb2+ concentration, root morphology index and the activity of antioxidant enzyme increased first and then decreased. Root morphology index reached the maximum in 50 mg/L Pb2+ concentration. B. subtilis QM3 clearly promoted the growth of the root and the antioxidant enzyme activity (p 0.05). Without Pb stress, B. subtilis QM3 had the best improving effect on root morphology. When Pb2+ concentration was 50 mg/L, superoxide dismutase (SOD) and ascorbate peroxidase (APX) reached the maximum. SOD activity, compared with CK, B1, B2 and B3 respectively, increased by 8.05%, 27.41% and 9.79%. APX activity, compared with CK, B1, B2 and B3 respectively, increased by 52.70%, 111.15% and 14.16%. Catalase (CAT) and peroxidase (POD) reached the maximum at the Pb2+ concentration was 500 mg/L. CAT activity, compared with CK, B1, B2 and B3 respectively, increased by 59.93%, 83.46% and 70.59%. POD activity, compared with CK, B1, B2 and B3 respectively, increased by 2.88%, 10.11% and 7.67%. Result suggested that B. subtilis QM3 could improve root growth and antioxidant enzyme activity of the wheat root under lead stress.展开更多
Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of e...Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 -?35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 -?35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.展开更多
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses ...The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.展开更多
基金supported by the National Natural Science Foundation of China(30800131)the Fundamental Research Funds for the Central Universities, China(2012ZYTS043)
文摘The polyphagous B-biotype of Bemisia tabaci (Gennadius) has demonstrated a high capacity to adapt to numerous hosts from diverse plant families. To illustrate induced responses by the host plant, biochemical research on eight plant-insect interaction correlative enzymes, representing detoxifying, antioxidant and digestive pathways, were investigated. Transferring whitefly adults to Zhongmian 23 from the pre-adapted host Zhongmian 41 induced activities of carboxylesterase (by 1.80-fold), glutathione S-transferase (by 3.79-fold), proteinase (by 1.62-fold) and amylase (by 2.41-fold) activities, hut decreased polyphenol oxidase (by 1.89-fold) and peroxidase (by 1.88-fold). However, transferring whitefly adults to the favorite host abutilon from Zhongmian 41 was associated with increased activities of cytochrome P450 monooxygenase (by 1.61-fold) and amylase (by 1.42-fold), and decreased activities of polyphenol oxidase (by 2.96-fold) and peroxidase (by 2.07-fold). Our results, together with previous studies, proved that multiple pathways are involved in coping with host shifts by polyphagous herbivores, and the taxonomic status and preference of the host transferred would affect which pathway would be induced. These results would represent a key challenge in developing long-term sustainable insect control strategies.
基金supported by grants from the National Natural Science Foundation of China (30901943)the Program for New Century Excellent Talents in University (NCET-04-0437)+1 种基金the E-institute of Shanghai Municipal Education Commission (E03008)the Innovative Research Team in Universities of Shanghai Municipal Education Commission
文摘BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30271183).
文摘BACKGROUND: 10-23 DNA enzyme is one kind of de-oxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2. 2. 15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A1816UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km,Kcat and Kcat/ Km for Drz-HBV-C-9, were 1.4 ×10-9 mol, 1.6 min-1 and 1.1 × 109 mol-1 · min-1, respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.
文摘AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB.
基金Supported by CNPq,No.460334/2014-0FAPEMIG,No.CDS-PPM-00555-15(to Simoes e Silva AC)2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation,No.25414(to Miranda AS)
文摘The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.
文摘B vitamins are enzyme cofactors that play an important role in energy metabolism.The aim of this study was to elucidate whether B vitamin administration can reduce body weight(BW)gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet.Fifty rats were randomly assigned to one of the following five groups:control group(C),including rats fed on standard rat chow;four treatment groups(H0,H1,H2,and H3),in which rats were fed on a high-fat diet.Rats in the H1 group were treated daily with 100 mg/kg BW thiamine(VB1),100 mg/kg BW riboflavin(VB2),and 250 mg/kg BW niacin(VPP);rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine(VB6),100 mg/kg BW cobalamin(VB12),and 5 mg/kg BW folate(FA);and rats in the H3 group were treated daily with all of the B vitamins administered to the H1 and H2 groups.After 12 weeks,the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the H1 and C groups,respectively,which were significantly less than the changes in the H0 group(285.2±14.8 g,P〈0.05).In the H0 group,the plasma total cholesterol(CHO)and triglyceride(TG)levels were 1.59±0.30 mmol/L and 1.55±0.40 mmol/L,respectively,which were significantly greater than those in the H1 group(1.19±0.18 mmol/L and 0.76±0.34 mmol/L,respectively,P〈0.05).The activities of transketolase(TK),glutathione reductase,and Na^+/K^+adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the H0 group(P〈0.05).Furthermore,the glucose-6-phosphate dehydrogenase,pyruvic acid kinase,and succinate dehydrogenase activities also were increased after treatment with B vitamins.Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats,thus possibly providing potential benefits to humans.
基金Supported by Key Project of Chinese Ministry of Science and Technology,No.2012ZX10002007 and No.2013ZX10002001National Natural Science Foundation of China,No.81171579,No.81201287 and No.81371832Science and Technology Development Plan of Shandong Province,China,No.2014GSF118068
文摘AIM: To evaluate tumor necrosis factor-α converting enzyme(TACE) methylation status in patients with chronic hepatitis B(CHB).METHODS: Eighty patients with hepatitis B e antigen(HBe Ag)-positive CHB, 80 with HBe Ag-negative CHB, and 40 healthy controls(HCs) were randomly enrolled in this study. Genomic DNA was extracted from peripheral blood mononuclear cells and methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The clinical and laboratory parameters were collected.RESULTS: One hundred and thirty of 160 patients with CHB(81.25%) and 38 of 40 HCs(95%) displayed TACE promoter methylation. The difference was significant(χ2 = 4.501, P < 0.05). TACE promoter methylation frequency in HBe Ag-positive CHB(58/80, 72.5%) was significantly lower than that in HBe Ag-negative CHB(72/80, 90%; χ2 = 8.041, P < 0.01) and HCs(χ2 = 8.438, P < 0.01). However, no significant difference was observed in the methylation frequency between HBe Agnegative CHB and HCs(χ2 = 0.873, P > 0.05). In the HBe Ag-positive group, TACE methylation frequency was significantly negatively correlated with HBe Ag(r =-0.602, P < 0.01), alanine aminotransferase(r =-0.461, P < 0.01) and aspartate aminotransferase(r =-0.329, P < 0.01). CONCLUSION: Patients with HBe Ag-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBe Ag seroconversion.
文摘Lead (Pb) is an environmental pollutant extremely toxic to plants and other living organisms including humans. In order to research the relieve effect of Bacillus subtilis QM3 on wheat roots (Triticum aestivum L.), after wheat seeds germination for two days, wheat root caused, the experimental materials were divided into four large groups and each large group was placed in 6 petri dishes as six small groups, and then four large groups respectively cultivated with sterile water (CK), 108 CFU/ml B. subtilis QM3 (B1), 107 CFU/ml B. subtilis QM3 (B2) and 106 CFU/ml B. subtilis QM3 (B3) for 2 days, after that stressed with lead nitrate, Pb (NO)2, Pb2+ concentration calculation at five concentrations (50, 250, 500, 1000, 2000 mg/L), sterile water and different Pb2+ concentration liquid respectively cultivated the 6 small groups in each large group measuring root morpholog and assaying changes of antioxidant enzyme activity. The results showed that: with the increase of the Pb2+ concentration, root morphology index and the activity of antioxidant enzyme increased first and then decreased. Root morphology index reached the maximum in 50 mg/L Pb2+ concentration. B. subtilis QM3 clearly promoted the growth of the root and the antioxidant enzyme activity (p 0.05). Without Pb stress, B. subtilis QM3 had the best improving effect on root morphology. When Pb2+ concentration was 50 mg/L, superoxide dismutase (SOD) and ascorbate peroxidase (APX) reached the maximum. SOD activity, compared with CK, B1, B2 and B3 respectively, increased by 8.05%, 27.41% and 9.79%. APX activity, compared with CK, B1, B2 and B3 respectively, increased by 52.70%, 111.15% and 14.16%. Catalase (CAT) and peroxidase (POD) reached the maximum at the Pb2+ concentration was 500 mg/L. CAT activity, compared with CK, B1, B2 and B3 respectively, increased by 59.93%, 83.46% and 70.59%. POD activity, compared with CK, B1, B2 and B3 respectively, increased by 2.88%, 10.11% and 7.67%. Result suggested that B. subtilis QM3 could improve root growth and antioxidant enzyme activity of the wheat root under lead stress.
文摘Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 -?35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 -?35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
基金Supported by the Heilongjiang Administration of Traditional Chinese Medicine(ZHY2020-078)the Education Department of Heilongjiang Province(SJGY20210830)。
文摘The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.