Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer's disease / 中西医结合学报

OBJECTIVE@#Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer's disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA.@*METHODS@#To generate a validated AD model, oligomeric amyloid-β@*RESULTS@#The learning and memory deficits of Aβ@*CONCLUSION@#This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ

Study on drug-target binding kinetics profiles of flavonoids in Chrysanthemum morifolium and xanthine oxidase / 中国中药杂志

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.

Simulation Analysis of Occupancy Rates of Baicalein， Quercetin and Galangin on Target Sites of Xanthine Oxidase / 中国实验方剂学杂志

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase <italic>in vivo</italic>. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by <italic>in vitro</italic> enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model <italic>in vivo</italic> was established. Result:The IC₅₀values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate <italic>in vivo</italic> of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% <italic>in vivo</italic> lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% <italic>in vivo </italic>lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and <italic>in vivo</italic> pharmacokinetic curves can effectively evaluate the <italic>in vivo</italic> inhibitory activity of compounds against the target.

Differences on geographic distribution of rabies virus lineages in China / 中华流行病学杂志

Objective To study the lineages of rabies virus and the epidemic characteristics in different provincial populations of China,to provide information for the development of control and prevention measures in each respective provinces.Methods Full length N and G genes and full-genome of epidemic strains of rabies virus collected in China were downloaded from GenBank and combined with newly sequenced strains by our lab.Each strain was classified under six lineages of China rabies by constructing phylogenetic trees based on the N or G sequences.Numbers of strains and lineages in each province were counted and compared.Results Six lineages (China Ⅰ-Ⅵ) were prevalent in China,with 4 found in Yunnan and Hunan.In 6 provinces,including Henan and Fujian,3 lineages were found.In 8 provinces,including Shanghai and Jiangxi,2 lineages were found Only 1 lineage,were found in Beijing,Tianjin and other 12 provinces.the China Ⅰ,was the dominant one in 25 provinces.In recent years,China Ⅲ had been found in wild animals and spread over livestock in Inner Mongolia and Xinjiang areas.Qinghai and Tibet had been influenced by China Ⅳ,which also been found in wild animals of Inner Mongolia and Heilongjiang.Conclusion There had been obvious differences in lineages and strain numbers of rabies virus identified in different provinces in China.

Differences on geographic distribution of rabies virus lineages in China / 中华流行病学杂志

Objective To study the lineages of rabies virus and the epidemic characteristics in different provincial populations of China,to provide information for the development of control and prevention measures in each respective provinces.Methods Full length N and G genes and full-genome of epidemic strains of rabies virus collected in China were downloaded from GenBank and combined with newly sequenced strains by our lab.Each strain was classified under six lineages of China rabies by constructing phylogenetic trees based on the N or G sequences.Numbers of strains and lineages in each province were counted and compared.Results Six lineages (China Ⅰ-Ⅵ) were prevalent in China,with 4 found in Yunnan and Hunan.In 6 provinces,including Henan and Fujian,3 lineages were found.In 8 provinces,including Shanghai and Jiangxi,2 lineages were found Only 1 lineage,were found in Beijing,Tianjin and other 12 provinces.the China Ⅰ,was the dominant one in 25 provinces.In recent years,China Ⅲ had been found in wild animals and spread over livestock in Inner Mongolia and Xinjiang areas.Qinghai and Tibet had been influenced by China Ⅳ,which also been found in wild animals of Inner Mongolia and Heilongjiang.Conclusion There had been obvious differences in lineages and strain numbers of rabies virus identified in different provinces in China.