Interactions between model target peptide melittin (ME) and Euplotes octocarinatus centrin (EoCen) were investigated by fluorescence spectra, circular dichroism (CD) spectra and native polyacrylamide gel electrophores...Interactions between model target peptide melittin (ME) and Euplotes octocarinatus centrin (EoCen) were investigated by fluorescence spectra, circular dichroism (CD) spectra and native polyacrylamide gel electrophoresis (PAGE). In 0.1 mol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (Hepes) and 150 mmol/L NaCl at pH 7.4, EoCen and isolated short C-terminal domain of EoCen (SC-EoCen) form 1:1 peptide:protein complexes. However, no detectable signal changes can be observed while isolated N-terminal domain of EoCen (N-EoCen) or isolated long C-terminal domain of EoCen (LC-EoCen) was added into solution of ME. The interaction between EoCen and ME is specified exclusively for the short C-terminal domain of EoCen. On the basis of fluorescence titration curves, the conditional binding constants of ME with EoCen and SC-EoCen were calculated to be logKME-EoCen = 6.81±0.33 and log- KME-SC-EoCen = 6.51±0.45, respectively.展开更多
OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage ...OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage for 26 weeks, at doses of 300, 1250, or 2500 mg·kg-1·d-1 respectively. The rats were euthanized at the end of 13 and 26 weeks daily oral dosing and following 4 weeks of recovery time. The changes of hematology, urinary, blood biochemistry and histomorphology were examined at each time point and focus on liver function and histological changes.RESULTS: When SBE at a dose of up to 2500 mgkg-1 d-1 was fed to male and female rats for 2··6 weeks, the liver tissue showed some inflammatory change that predominated by leukocyte infiltrationbut returned to normal after withdrawal. In addition, high-dose SBE treatment of 26 weeks in rats,glucose, electrolyte and lipid levels also have some changes. In addition, there are no other functional or organic lesions related to SBE treatment.CONCLUSIONS: Long-term and high-dose SBE may cause liver damage, however, the structural damage of the liver can be restored after the ethanol extract stopping. SBE will be well-tolerated for long-term use as a drug or health food, but in order to ensure drug safety, liver function, and serum glucose, electrolyte and lipid levels should be monitored when using SBE long term.展开更多
Ciliate Euplotes octocarinatus centrin (EoCen) is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor protein calmodulin.The first amino acid of the Ca2+-binding loops found in the EF...Ciliate Euplotes octocarinatus centrin (EoCen) is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor protein calmodulin.The first amino acid of the Ca2+-binding loops found in the EF-hand calcium-binding proteins is a highly conserved aspartic acid residue.The D37K mutant was produced to elucidate the metal binding role of the first aspartic acid of the EF-loop I of EoCen.Aromatic-sensitized Tb3+fluorescence results indicated that the metal binding ability of loop I was lost due to the D37K mutation.Based on fluorescence titration curves of Lu2-D37K,the conditional binding constants of the EoCen loop II were quantitatively found to be KII=(1.61±0.04)×105 L mol-1 and KII=(3.52±0.08)×102 L mol-1 with Tb3+ and Ca2+,respectively.Using 2-p-toluidinylnaphthalene-6-sulfonate as a hydrophobic probe,exposure of the hydrophobic surface upon metal binding was found to be significantly reduced for the metal ion-saturated EoCen D37K mutant.展开更多
OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats.METHODS: Oroxylumindicum(L.) Vent extract was administrated to male and female rats by gavage once daily a...OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats.METHODS: Oroxylumindicum(L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg·kg-1·d-1.The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of13, 26 weeks of administration and 4 weeks of recovery.RESULTS: No treatment related adverse effect shappened on rats' general status, body weight, food consumption, urinary index and histomorphologyexamination. Although during the administration,in some rats of extract's groups, the value of Red blood cell count(RBC), white blood cell counts(WBC), hemoglobin(HGB), haematocrit(HCT) and K iron were decreased, and biochemistry index,such as glucose(GLU), triglyceride(TG), alanine transaminase(ALT) and blood urea nitrogen(BUN)were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks.CONCLUSION: The administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg(equals to 75 times of clinical dose) is well toleratedfor both genders without significant toxicity within the administration duration in this study.展开更多
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20371031 and 20771068)the Natural Science Foundation of Shanxi Province (Grant No. 2007011024) Young Science Foundation of Shanxi University
文摘Interactions between model target peptide melittin (ME) and Euplotes octocarinatus centrin (EoCen) were investigated by fluorescence spectra, circular dichroism (CD) spectra and native polyacrylamide gel electrophoresis (PAGE). In 0.1 mol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (Hepes) and 150 mmol/L NaCl at pH 7.4, EoCen and isolated short C-terminal domain of EoCen (SC-EoCen) form 1:1 peptide:protein complexes. However, no detectable signal changes can be observed while isolated N-terminal domain of EoCen (N-EoCen) or isolated long C-terminal domain of EoCen (LC-EoCen) was added into solution of ME. The interaction between EoCen and ME is specified exclusively for the short C-terminal domain of EoCen. On the basis of fluorescence titration curves, the conditional binding constants of ME with EoCen and SC-EoCen were calculated to be logKME-EoCen = 6.81±0.33 and log- KME-SC-EoCen = 6.51±0.45, respectively.
基金Supported by Major National Science and Technology Projects of China(No.2015ZX09501004No.2014 ZX09304307001+1 种基金No.2014ZX09201022-004)Beijing Science and Technology Projects(No.Z161100004916025,No.Z151100000115012)
文摘OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage for 26 weeks, at doses of 300, 1250, or 2500 mg·kg-1·d-1 respectively. The rats were euthanized at the end of 13 and 26 weeks daily oral dosing and following 4 weeks of recovery time. The changes of hematology, urinary, blood biochemistry and histomorphology were examined at each time point and focus on liver function and histological changes.RESULTS: When SBE at a dose of up to 2500 mgkg-1 d-1 was fed to male and female rats for 2··6 weeks, the liver tissue showed some inflammatory change that predominated by leukocyte infiltrationbut returned to normal after withdrawal. In addition, high-dose SBE treatment of 26 weeks in rats,glucose, electrolyte and lipid levels also have some changes. In addition, there are no other functional or organic lesions related to SBE treatment.CONCLUSIONS: Long-term and high-dose SBE may cause liver damage, however, the structural damage of the liver can be restored after the ethanol extract stopping. SBE will be well-tolerated for long-term use as a drug or health food, but in order to ensure drug safety, liver function, and serum glucose, electrolyte and lipid levels should be monitored when using SBE long term.
基金supported by the National Natural Science Foundation of China(20771068,20901048)the Ph.D Programs Foundation of Ministry of Education of the People’s Republic of China(20091401110007)the Natural Science Foundation of Shanxi Province(2007011024)
文摘Ciliate Euplotes octocarinatus centrin (EoCen) is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor protein calmodulin.The first amino acid of the Ca2+-binding loops found in the EF-hand calcium-binding proteins is a highly conserved aspartic acid residue.The D37K mutant was produced to elucidate the metal binding role of the first aspartic acid of the EF-loop I of EoCen.Aromatic-sensitized Tb3+fluorescence results indicated that the metal binding ability of loop I was lost due to the D37K mutation.Based on fluorescence titration curves of Lu2-D37K,the conditional binding constants of the EoCen loop II were quantitatively found to be KII=(1.61±0.04)×105 L mol-1 and KII=(3.52±0.08)×102 L mol-1 with Tb3+ and Ca2+,respectively.Using 2-p-toluidinylnaphthalene-6-sulfonate as a hydrophobic probe,exposure of the hydrophobic surface upon metal binding was found to be significantly reduced for the metal ion-saturated EoCen D37K mutant.
基金Supported by Major National Science and Technology Projectsof China(2015ZX09501004 2014ZX09304307001+1 种基金2014ZX09201022-004)Beijing Science and Technology Projects(Z161100004916025,Z151100000115012)
文摘OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats.METHODS: Oroxylumindicum(L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg·kg-1·d-1.The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of13, 26 weeks of administration and 4 weeks of recovery.RESULTS: No treatment related adverse effect shappened on rats' general status, body weight, food consumption, urinary index and histomorphologyexamination. Although during the administration,in some rats of extract's groups, the value of Red blood cell count(RBC), white blood cell counts(WBC), hemoglobin(HGB), haematocrit(HCT) and K iron were decreased, and biochemistry index,such as glucose(GLU), triglyceride(TG), alanine transaminase(ALT) and blood urea nitrogen(BUN)were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks.CONCLUSION: The administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg(equals to 75 times of clinical dose) is well toleratedfor both genders without significant toxicity within the administration duration in this study.
