Analysis on Evolution of Ancient Documents of Xiehuangsan / 中国实验方剂学杂志

Xiehuangsan， derived from QIAN Yi's Key to Therapeutics of Children's Diseases， consists of 5 medicines， namely Gypsum Fibrosum，Gardeniae Fructus，Saposhnikoviae Radix，Pogostemonis Herba and Glycyrrhizae Radix et Rhizoma. It is used to treat children with spleen heat and tongue scratching. With the clinical use of later generations of physicians，the scope of diseases and syndromes of this prescription was gradually expanded，including aphthous bad breath，dry lips，yellow eyes，and sweet mouth. Modern doctors used this prescription to treat children with anorexia，constipation，allergic purpura，tic disorder， and other diseases. At present，more and more attention has been paid to the research of classical famous prescriptions. At the same time，the application of classical famous prescriptions of traditional Chinese medicine（TCM） must be researched and verified in ancient literature. Therefore，it has become important contents in the study of classic prescriptions that researching the source of prescriptions from the ancient books，combing and analyzing literature，and studying the evolution rules of indications，preparations，methods of administration and taboos.The author searched a variety of ancient Chinese medicine databases and collected the relevant documents related to Xiehuangsan in ancient medical books. A total of 242 pieces of relevant ancient document data were obtained，involving 131 types of ancient Chinese medicine books. Through combing the relevant records of historical documents，this paper analyzes and researches the historical evolution of Xiehuangsan，the source and composition of the prescriptions，the indications，the dosage，the textual research of Chinese herbal medicine and the determination of the basis，and the method of prescription preparation and administration，etc. The historical changes of Xiehuangsan and its internal relations are expected to provide literature references and theoretical basis for the modern development and research of Xiehuangsan.

Tau-Induced Ca/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation / 神经科学通报·英文版

Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca concentration with a simultaneous increase in the phosphorylation of Ca/calmodulin-dependent protein kinase IV (CaMKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca/CaMKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation of the Ca/calmodulin complex abolished the okadaic acid-induced tau hyperphosphorylation in the nuclear fraction. We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca/CaMKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca concentration may induce a self-perpetuating harmful loop to promote neurodegeneration.

Effects of salidroside on proliferation of bone marrow mesenchymal stem cells / 中国实验血液学杂志

This study was aimed to investigate the effect of salidroside on proliferation of bone marrow mesenchymal stem cells (MSC) and their secretion of stem cell factor (SCF). MSC were isolated and amplified in vitro via density gradient centrifugation and adherence screening method. MCS were identified by flow cytometry and osteogenic/adipogenic induction. The effects of salidroside on cell proliferation, cell cycle and the SCF secretion of MSC were detected by flow cytometry. The results showed that the salidroside could induce the proliferation of MSC, peaked at the concentration of 1.5 mg/ml and in a time-dependent manner (in 24 h, 48 h and 72 h). Salidroside at 1.5 mg/ml could more effectively increase the percentage of cells in S and G1/M phase. Co-cultured with salidroside at the concentration of 1.5 mg/ml for 48 h, the SCF and the expression levels of SCF mRNA in co-culture supernatant were both significantly increased (P < 0.01). It is concluded that salidroside in a range of certain concentration can obviously promote the proliferation of MSC and increase the expression and secretion of SCF.

Effect of salidroside on apoptosis of bone marrow mesenchymal stem cells induced by ara-C / 中国实验血液学杂志

The purpose of this study was to investigate the effect of salidroside on human bone marrow mesenchymal stem cell (hBMMSC) apoptosis induced by cytarabine C (Ara-C) and its mechanism, hBMMSC were cultured in vitro and isolated by Fircoll density gradient centrifugation; cell surface antigens were measured by flow cytometry; the osteogenic and adipogenic differentiation of MSC was tested and evaluated by specific staining methods. The proliferation and apoptosis of cells exposed to Ara- C were detected by MTT and flow cytometry respectively. The experiments were divided into 4 groups: control group, Ara-C group, salidroside group and Ara-C+salidroside group. The mRNA expression of BCL-2 and BAX was assayed by RT-PCR. The results showed that the adherent cells displayed spindle and fibroblast cell-like shape; the hBMMSC expressed CD44, CD71 and HLA-ABC, not expressed CD34, CD45 and HLA-DR; the hBMMSC successfully differentiated into osteogenic and adipogenic lineages, which showed mineralization with von Kossa staining. Furthermore, liquid vacuoles were detected by oil red O staining; Ara- C exhibited a less inhibitory effect on the proliferation of hBMMSC treated with salidroside. The apoptosis of hBMMSC treated with salidroside were significantly higher as compared with control group (P < 0.05); RT-PCR results demonstrated that the BCL-2 expression was significantly down regulated but BAX mRNA expressions was up-regulated in Ara- C group as compared with those in the control group. Salidroside significantly inhibited the apoptosis of MSC and reversed the mRNA expression of BCL-2 and BAX. It is concluded that salidroside can inhibit the apoptosis of hBMMSC induced by Ara-C, its mechanism may be related with the regulation of BCL-2/BAX expression.