Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression / 中国天然药物

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

Mechanism of Kai Xin San in the treatment of Alzheimer's disease based on network pharmacology / 药学学报

The study was designed to explore the active components and mechanism of Kai Xin San in the treatment of Alzheimer's disease (AD) based on network pharmacology. All targets related to AD were researched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Therapeutic Targets Database (TTD). The common targets obtained by two databases were determined as candidate proteins involved in AD. All active components related to Kai Xin San were researched from ADME (absorption, distribution, metabolism and excretion). PharmMapper was used to obtain the primary candidate targets of Kai Xin San. The corresponding gene name of each target protein was obtained from the UniProt database and selected human target proteins. Finally, the target proteins related to AD by Kai Xin San were acquired; Cytoscape 3.5.1 was used to construct the topology analysis for the active ingredient-AD target interaction network of Kai Xin San. According to STRING database and DAVID annotation databases, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the targets was performed. The network pharmacology analysis results were verified by Discovery Studio molecular docking software. There were 31 components meeting the conditions of ADME and 8 targets relating to AD. Thirteen kinds of biological process, 7 related to molecular function and 11 related to cellar components, were included in 31 GO entries. There were 5 KEGG pathways, involving the calcium signaling pathway and PI3K-Akt signaling pathway. The docking results of Discovery Studio showed that active ingredients of Kai Xin San and the positive controls all have good binding activity with important targets. In conclusion, the Kai Xin San as applied for treating AD has the advantages of multi-components and targets, to investigate the active components and mechanism of Kai Xin San for treating AD based on network pharmacology to eludicate possible studies of the mechanisms of action.

The study of the protective effect of panoxadiol on Alzheimer’s disease cells based on network pharmacology / 中国药理学通报

Aim To explore the therapeutic effects of main active compounds of panaxadiol ( PD ) in on Alzheimer’s disease ( AD) via network pharmacologi-cal analysis and Mmolecular docking. Methods A to-tal of 107 prescriptions for AD treatment were screened by using network pharmacology, screening for the high-est frequency of ginseng and its target for AD. Use mo-lecular docking technology was used to find components with the highest score for non-receptor tyrosine kinase ( FYN) docking. Then we successfully estimatedestab-lished AD cell model with overexpressinged APP pro-teins in vitro. Next,the cell viability was detected by MTT assay,the cell damage was detected by LDH as-say,the apoptosis and intracellular Ca2+concentration were detected by flow cytometry, and phosphorylated FYN protein expression was detected by Western blot detection of . phosphorylated FYN protein expression. Results Eighteen active components of Gginseng and 29 AD-related targets were screened by the method of network pharmacology. The results of molecular doc-king showed that PD had strong binding effects with FYN. The results showed that PD could increase the survival rate of cells,reduce the release of LDH,reduce apoptosis,and improve AD cells’ intracellular Ca2+o-verload and reduce the expression of FYN-Y416 pro-tein. Conclusion The experimental results of network pharmacology were are verified and the protective effect of PD on AD may be related to inhibition of FYN signa-ling pathway.

Difference in effect between asthma-based mouse model and Stemona tuberosa extracts / 中国中药杂志

In this study, OVA-induced asthma mice was taken as the model, and orally administered with different concentration of ethanol extracts of crude and processed Stemona tuberosa, in order to determine the cytokine level released from Th1 and Th2 in splenocytes. RT-PCR was carried out to determine the genetic expression of T-bet/GATA-3 in lung, and compare the differentiation between ethanol extracts of crude and processed S. tuberosa in therapeutic effect on asthma in mice. According to the results, compared with the crude samples, processed samples significantly increased the levels of inflammatory factor INF-gamma (P < 0.05) and decreased IL-5 (P < 0.05) in splenocytes. According to the RT-PCR results, the administration of processed samples could increase the ratio of T-bet/GATA-3 (P < 0.05). The experiment showed that ethanol extracts of both crude and processed S. tuberosa could treat asthma by regulating Th1/Th2 ratio, but processed samples showed more notable effect. This indicated that crude and processed S. tuberosa had significant pharmacological difference. Therefore, it was more rational to apply processed S. tuberosa in clinical treatment of asthma and chronic cough, which layed a foundation for further revealing the processing mechanism of S. tuberosa.

Mutation analysis of the HBV reverse transcriptase in nucleos(t)ide-treated patients with chronic HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To characterize genotypic resistance within HBV RT region in chronic hepatitis B (CHB) patients with nucleos(t)ide analogue (NA) treatment.</p><p><b>METHODS</b>Serum samples of 229 CHB patients with NA treatment were obtained. Full-length HBV RT sequences were amplified, sequenced and analyzed, on the following NA resistant (NAr) mutations belonging to different NAr pathways.</p><p><b>RESULTS</b>Among 229 HBV isolates, 14.41% (33/229) and 85.59% (196/229) were genotype B and C, respectively; and the patients with HBV genotype C may be more susceptible to develope resistant mutations than patients with HBV genotype B(chi2 = 2.95, P < 0.05). NAr mutations were detected in 63 CHB patients. Mutations were not found at rtI169, rtT184, rtA194 or rtS202. RtM204 mutations were detected at the highest frequency among 63 mutants (40/63, 63.49%) and found to display 11 combination mutation patterns, in which rtM204I were associated with rtL80I/V and rtL180M, and rtM204V were associated with rtL1l80M, respectively. Conclusions There are complicated mutation patterns in the HBV RT region for chronic hepatitis B (CHB) patients with nucleos(t)ide analogue (NA) treatment. RtM204V/I mutation was the highest.</p>

Drug resistance, genotype, and serotype of hepatitis B virus in nucleos(t)ide analogue naive patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate drug resistance, genotype and serotype of hepatitis B virus (HBV) in nucleos(t)ide analogue (NA) naive patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>Full-length reverse transcriptase region of HBV DNA was amplified by semi-nested polymerase chain reaction from 97 NA-naive CHB patients, and the PCR product was sequenced, and analyzed to screen 11 classical antiviral drug resistance mutation sites and to identify HBV genotypes, subgenotypes and serotypes.</p><p><b>RESULTS</b>Wild-type sequences were found at all of the 11 classical antiviral drug resistance mutation sites from all samples. The patients were infected with either genotype B (36.1%, 35/97) or C (63.9%, 62/97) HBV. The former were all belonged to subgenotype B2 strain; while the latter were divided further into subgenotype C2 (91.9%, 57/62), subgenotype C1 (6.5%, 4/62) and unknown subgenotype (1.6%, 1/62). The 71.9% (23/32) of HBV genotype B patients were born in southern China, while 81.6% (40/49) of HBV genotype C patients were from northern China, showing a clear geographic distribution (Chi-square test = 23.19, Probability value less than 0.01). Of 97 CHB patients, 59 (60.8%) were serotype adr associated with genotype C, while 37 (38.1%) were adw related to genotype B (subgenotype B2) (Chi-square test = 87.83, P less than 0.01).</p><p><b>CONCLUSION</b>The wild-type HBV strains prevail in NA-naive CHB patients, whose HBV genotypes, subgenotypes and serotypes are associated with their places of birth.</p>

Effects of caldesmon, calponin, and tropomyosin on the Mg2+-ATPase activities of smooth muscle myosin / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To test whether in the absence of actin, actin-binding proteins such as caldesmon, calponin, and tropomyosin interact with the myosin of unphosphorylation, Ca2+-dependent phosphorylation (CDP), and Ca2+-independent phosphorylation (CIP) and stimulate myosin Mg2+-ATPase activities.</p><p><b>METHODS</b>Mg2+-ATPase activities were measured to evaluate the effects of caldesmon, calponin, and tropomyosin on the myosin in unphosphorylation, CDP by myosin light chain kinase (MLCK), and CIP by MLCK.</p><p><b>RESULTS</b>(1) At different incubation-time, i.e., 5, 10, 20, 40, and 60 minutes, the highest Mg2+-ATPase activity was observed when myosin was in the state of CDP, the medium was CIP of myosin, and the lowest was the unphosphorylated myosin. (2) In the absence of caldesmon, calponin, and tropomyosin, the Mg2+-ATPase activities from high to low were in the following order: CDP, CIP, and unphosphorylated myosin. However, in the presence of caldesmon, calponin, and tropomyosin, the order of relative value of Mg2+-ATPase activities from high to low was unphosphorylated, CIP, and CDP of myosin respectively compared to the corresponding controls.</p><p><b>CONCLUSIONS</b>The results propose that caldesmon, calponin, and tropomyosin are capable of stimulating Mg2+-ATPase activity of smooth muscle myosin in Ca2+-independent manner, since Ca2+ is not obligating for the stimulating effects of the three proteins. The common characteristic of the three proteins is that when myosin activities are low, their activations are relatively strong and this property might be involved in smooth muscle tension keeping.</p>