The effect of recombinant human phospholipase D2(rhPLD2)in vivo was investigated on the secretion of serum glycosyl phosphatidylinositol-specific phospholipase D(GPI-PLD)in guinea pigs of chronic asthma．Ater treating the guinea pigs attacked by chronic asthma with rhPLD2,the GPI-PLD activity detection was canrried out by phase separation of human placental alkaline phosphatase in Triton X-114．Compared with the healthy guinea pigs(NS group),the serum GPI-PLD in the guinea pigs of chronic asthma are much higher than that of control groups,P≤0．01．Our results showed that rhPLD2 could significantly reduce the secretion of GPI-PLD when the guinea pigs were attacked by chronic asthma．

Objective To investigate the effects of hydrogen gas on the myocardial injury in rats with endotoxemia.Methods Forty-eight healthy male Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 4 groups (n =12 each ):control group (group C ),hydrogen gas control group (group HC ),endotoxemia group (group E) and hydrogen gas + endotoxemia group (group LH).Endotoxemia was induced by intraperitoneal lipopolysaccharide (LPS) 20 mg/kg in groups E and LH,while the equal volume of normal saline was given in groups C and HC.After LPS administration,the rats were exposed to the air containing 2％ hydrogen gas for 6 h in groups HC and LH,and the rats were exposed to the air for 6 h in groups C and E.Blood samples were taken from the abdominal aorta after 6 h inhalation of hydrogen gas to determine the serum level of cTnI.The hearts were then removed to determine the content of TNF-α and IL-6 and expression of phosphorylated nuclear factor κB ( NF-κB) inhibitory protein (p-IκB-α) and p38 mitogen-activated protein kinase (p-p38MAPK) in the myocardial tissues.Results Compared with group C,no significant change was found in the levels of cTnI,TNF-α and IL-6 and expression of p-IκB-α and p-p38MAPK in group HC ( P ＞ 0.05),and the levels of cTnI,TNF-α and IL-6 were significantly increased and the expression of p-IκB-α and p-p38MAPK was up-regulated in groups E and LH ( P ＜ 0.05).Compared with group E,the levels of cTnI,TNF-α and IL-6 were significantly decreased and the expression of p-IκB-α and p-p38MAPK was down-regulated in group LH ( P ＜ 0.05).Conclusion Hydrogen gas can reduce the myocardial injury in rats with endotoxemia,and inhibition of the p38MAPK and NF-κB pro-inflammatory pathway and reduction of the inflammatory response of myocardial tissues are involved in the mechanism.

To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Models, Molecular ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; Quantitative Structure-Activity Relationship

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

Humans ; Pneumoconiosis ; diagnostic imaging ; Radiographic Image Enhancement ; Radiography ; methods

By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents ; chemistry ; pharmacology ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Mineralocorticoid Receptor Antagonists ; chemistry ; pharmacology ; Models, Molecular

Objective:To study the biologic function of rhPLD2 mutation form.Methods:To adapt the guinea pig chronic asthma model was induced by OVA, the functions of rhPLD2 on PAF was observed through the assay of platelet congregating.Results:rhPLD2 remarkably reduced the lever of PAF in the serum of guinea pig chronic asthma model; compares with the NS group, the P

Objective:To investigate the prevalence of fever after intravenous injection of for the first time in osteoporotic patients who have or haven’t taken bisphosphonates orally.Methods:Bone mineral density measurement was conducted of the osteoporotic patients using dual-energy X-ray absorptiometry method,and according to the WHO diagnostic criteria for osteoporosis,the patient whose T score was less than -2.5 was defined as osteoporosis.The data of 113 osteoporotic patients who received intravenous injection of zoledronic acid in our hospital for the first time were used for analysis.Among them,35 who had the history of oral bisphosphonates were defined as group A,and 78 who didn’t have the history of oral bisphosphonates were defined as group B (control group).Moreover,we also compared the preva-lences of fever between the patients.Pearson chi-square test was used to investigate the association be-tween oral bisphosphonates therapy and prevalence of fever,and binary logistic regression was used to an-alyze the impact factors of fever after intravenous injection of zoledronic acid.Results:Among the 35 pa-tients who had the history of oral bisphosphonates,nobody had high fever,and 2 patients had low or mo-derate degree of fever (5.71%).Among the 78 patients who didn’t have the history of oral bisphospho-nates,33 patients had fever (42.3%),15 with low fever,and 14 with moderate degree of fever,and 4 with high fever.Pearson chi-square test showed that the prevalence of fever between group A and group B had significant difference,and that differences of prevalence of fever between the outpatients and the inpa-tients was not statistically significant.Binary Logistic regression analysis showed that oral bisphosphonates medication history was a protective factor of fever,and with the increasing of previous oral bisphosphonates for one month,there was a reduction of fever for 23.1%.Conclusion:Patients who have the history of oral nitrogenous bisphosphonates alendronate have a significant reduction in prevalence of fever after intravenous injection of zoledronic acid for the first time.That is,oral nitrogenous bisphosphonates alendronate history is a protective factor of fever for patients with intravenous injection of zoledronic acid for the first time.

Objective To investigate the clinical treatment efficacy of mutabilis coated nasal ointment to postoperative nasal septal reconstruction.Methods After surgical reconstruction,116 cases were divided into the treatment group and control group ac-cording to random method,58 cases in each group.The treatment group was given mutabilis coated nasal ointment combine with physiological seawater nasal care device;the control group was only given physiological seawater nasal care device in the same time. The effects were observed for 6 months.Results The total effective rate of treatment group was higher than the control group (98.28%),the two groups had significant difference(P <0.05).Postoperative follow-up,the bleeding rate in the treatment group have no significant difference compared with the control group(P >0.05);the incidence of infection and cavity stricture in the treat-ment group were significantly lower than the control group(P <0.05).Conclusion The application of mutabilis coated nasal oint-ment can promote the wound healing of nasal cavity,but also can prevent the operation adhesion,and shorten repair time,so as to improve the clinical effect of operation.

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry