OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese pa...OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.展开更多
Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide ...Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide adenine dinucleotide （NAD）, which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin signaling, constituting a strong intrinsic defense system against various stresses. Most recently, we and others have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these bene- fits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators and ischemic conditioning are promising for stroke salvage and rehabilitation. Here, we discuss the current NAMPT data in the context of translational efforts for stroke treat- ment.展开更多
Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery...Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.展开更多
The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra hou...The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.展开更多
文摘OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.
文摘Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide adenine dinucleotide （NAD）, which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin signaling, constituting a strong intrinsic defense system against various stresses. Most recently, we and others have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these bene- fits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators and ischemic conditioning are promising for stroke salvage and rehabilitation. Here, we discuss the current NAMPT data in the context of translational efforts for stroke treat- ment.
文摘Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.
基金the National Natural Science Foundation of China(32273062,31973005)。
文摘The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.
