BACKGROUNDGlucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.

METHODSEighty hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment.

RESULTSImmunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.

CONCLUSIONSBoth the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

Aged ; Blotting, Western ; Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Lovastatin ; therapeutic use ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Nifedipine ; therapeutic use ; Receptors, Glucocorticoid ; metabolism

BACKGROUNDLactate dehydrogenase (LDH) is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B (LDHA and LDHB) genes following lovastatin treatment.

METHODSThe rat myocardial cell line H9c2(2-1) in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional (mRNA) level with quantitative real-time polymerase chain reaction (Q-RT-PCR), and at the translational (protein) level with immunoblotting.

RESULTSWhen compared with control levels, the LDHA mRNA went up by (151.65 ± 16.72)% (P = 0.0132) after 24 hours and by (175.28 ± 56.54)% (P = 0.0366) after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to (63.65 ± 15.21)% of control levels (P = 0.0117). After 24 hours of treatment with lovastatin, there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by (148.65 ± 11.81)% (P = 0.00969), while the protein levels of LDHB were down-regulated to (64.91 ± 5.47)% of control levels (P = 0.0192).

CONCLUSIONSLovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.

Animals ; Anticholesteremic Agents ; pharmacology ; Blotting, Western ; Cell Line ; Isoenzymes ; genetics ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Lovastatin ; pharmacology ; Myocytes, Cardiac ; drug effects ; enzymology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo establish a method of TLC identification for Dida commonly used in Tibetan medicine from different species.

METHODWith silica gel G as the stationary phase, and chloroform-methanol (40: 1) as mobile phase, oleanolic acid from different species of Dida was separated and identified.

RESULTOleanolic acid was detected in 70 kinds of Dida derived from the Gentianaceae Swertia, Halenia, Gentianopsis, Lomatogonium, and Saxifragaceae saxifrage, except for the saxifrage, there are some differences among different genera or subjection.

CONCLUSIONThis TLC method can be used for identification of oleanolic acid in Dida from different species except saxifrage.

Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; methods ; Drugs, Chinese Herbal ; chemistry ; Medicine, Tibetan Traditional ; methods ; Oleanolic Acid ; analysis ; chemistry ; Species Specificity

OBJECTIVETo observe the effect of pBBADs-OXM-transformed bifidobacteria on the body weight of obese mice.

METHODSB. longum was transformed with pBBADs-OXM by electroporation, and arabopyranose-induced oxyntomodulin expression by the bacterium was detected by ELISA. pBBADs-OXM-transformed bifidobacteria was administered orally obese mice on a daily basis with pBBADs-GFP-transformed bifidobacteria as the negative control, and the body weight changes of the mice were observed.

RESULTSOXM was detected by ELISA not only in the supernatant but also the precipitant of the transformed bacterial culture. The body weight of the obese mice fed with pBBADs-OXM-transformed bifidobacteria decreased significantly compared with that of the mice in the obese model group (P<0.05).

CONCLUSIONAdministration of pBBADs-OXM-transformed B.longum can reduce the body weight of obese mice.

Administration, Oral ; Animals ; Appetite Depressants ; administration & dosage ; metabolism ; Bifidobacterium ; genetics ; metabolism ; Body Weight ; drug effects ; Electroporation ; Escherichia coli ; genetics ; metabolism ; Mice ; Obesity ; drug therapy ; Oxyntomodulin ; administration & dosage ; biosynthesis ; genetics ; Random Allocation ; Recombinant Proteins ; administration & dosage ; biosynthesis ; genetics

OBJECTIVETo investigate the effect of the photodynamic therapy (PDT) with the new water-soluble metalloporphyrin compound on human prostate cancer PC-3 cells in vitro and the anticancer mechanism of PDT.

METHODSThe new water-soluble manganese, 5,10,15, 20-tetra (N-methyl4-pyridyl) porphinato (2-) tetraiodide salt, was synthesized. The PC-3 cells were treated with the compound of serial concentrations(0, 0.1, 1, 1.0 micromol/L) followed by irradiation of different dosages of visible light. The techniques of MTT and Annexin-V/propidium iodide double-labeled flow cytometry (FCM) were applied to measuring the inhibitory effect of the compound on the growth activity and apoptosis of the cells.

RESULTSWhen the metalloporphyrin compound concentration was within 10 micromol/L and the irradiation time was within 30 min, the water-soluble metalloporphyrin compound had a significant inhibitory effect on the proliferation of PC-3 cells and induced PC-3 cell apoptosis, and the effects depended greatly on metalloporphyrin concentration and illumination dosages. Higher concentrations and dosages induced the death of the majority of PC-3 cells.

CONCLUSIONThe PDT of the water-soluble metalloporphyrin compound followed by light irradiation has a distinctive killing effect on PC-3 cells in vitro, and the rates of proliferation inhibition and cell apoptosis are correlated with metalloporphyrin concentration and the dosages of light irradiation. The results suggest that the mechanism of metalloporphyrin PDT may be involved with the induction of apoptosis in human prostate cancer cells.

Apoptosis ; drug effects ; radiation effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Humans ; Male ; Metalloporphyrins ; pharmacology ; Photochemotherapy ; Prostatic Neoplasms ; pathology

OBJECTIVETo establish a method for determination of 10 ingredients such as gentiopicroside, sweroside, and mangiferin in India swertia, and settle the index components and their limits.

METHODBy Welch materials AQ-C18 column, determination was conducted by the gradient elution with methanol and 0.4% formic acid as mobile phase, with column temperature 30 degrees C, flow rate at 1.0 mL x min(-1), and 254 nm as the detection wavelength.

RESULTThe linear relatives of 10 ingredients were good. The method showed the high precision and good reproducibility, and recovery rates were between 97% and 103%. The ingredients of market com-modities varied greatly.

CONCLUSIONThis method is simple, sensitive, reproducible, and applicable to the determination of the main ingredients in India Swertia. Sweroside and mango glycosides were suggested as the index components for determination in Jia Di (Swertia chirayita), and their content limits are not less than 0.1%, 0.3%, respectively.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; standards ; Iridoid Glucosides ; analysis ; standards ; Medicine, Tibetan Traditional ; Quality Control ; Swertia ; chemistry

OBJECTIVETo evaluate the medicinal reasonableness and resource utilization of Dida from different species.

METHODWith common characteristic absorption peaks of HPLC fingerprints and SPSS cluster, the composition similarity of Dida from different species was evaluated.

RESULTThe composition similarity of HPLC fingerprints of 33 Dida samples from 15 species and 1 variety originated from Swertia, Halenia, Gentianopsis, Lomatogonium was difference. The original species can be clustered into four groups by the relative area of 10 common characteristic peaks of HPLC fingerprints. The compositions of four different genera are quite different.

CONCLUSIONBecause of containing iridoids, xanthones, and triterpenes which have liver protection and cholagogue functions, all of species from Swertia, Halenia, Gentianopsis and Lomatogonium in Gentianaceae are classified as Dida in Tibetan medicine. According to the composition difference among different species, the HPLC fingerprints established for Dida from different source are an effective means to identify nd control the quality of Dida.

Drugs, Chinese Herbal ; analysis ; Medicine, Tibetan Traditional ; Plants, Medicinal ; chemistry ; classification

OBJECTIVETo investigate the role of lysine-specific demethylase 1 (LSD1) in the process of THP-1 monocyte-to-macrophage differentiation.

METHODSQuantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 (IL-6) in THP-1 monocytes and THP-1-derived macrophages. Chromatin immunoprecipitation (ChIP) assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP-1 monocyte-to-macrophage differentiation. IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChIP assay in LSD1-knockdown THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 0, 4, 8, 12, and 24 hours. Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP-1 monocytes.

RESULTSThe expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation (P<0.01). LSD1 occupancy decreased and H3K4 methylation increased at IL-6 promoter during the differentiation. With knockdown of LSD1, H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points (all P<0.05, except 24 hours). The percentage of macrophages increased significantly in the THP-1 cells with LSD1 knockdown (P<0.05).

CONCLUSIONSLSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells. Suppression of LSD1-mediated H3K4 demethylation may be required for THP-1 monocyte-to-macrophage differentiation.

Cell Differentiation ; Cells, Cultured ; Dealkylation ; Histone Demethylases ; physiology ; Histones ; metabolism ; Humans ; Interleukin-6 ; genetics ; Macrophages ; cytology ; Monocytes ; cytology ; Promoter Regions, Genetic

The study is aimed to clarify the actual original plant, find out the usage status and the resource distribution of the Tibetan medicinal plant "Bangga". By using the way of the literatures survey, interview and investigation, it found out that the actual original plant of the Tibetan medicinal plant "Bangga" were the whole dried plant or the aerial part of Aconitum tanguticum or A. naviculare of Ranunculaceae, among which A. tanguticummainly distributed in Sichuan, Gansu, Qinghai, Tibet (Qamdo), and A. naviculare mainly distributed in Tibet. Sichuan, Gansu, Qinghai and other Tibetan areas mainly used the resources of A. tanguticum, Tibet (except the Qamdo area) mainly uses the A. naviculare, which resource was imminent in danger. Other species described in the literature were not used. It showed that the use of herbs related to their resources, it is recommended to strengthen the protection and guide the market.

This paper deals with the application of ultra-performance liquid chromatography tandem quadrupole time of flight mass spectrometry(UPLC-ESI-Q-TOF-MS/MS) method to rapidly determine and analyze the chemical constituents of methanol extract of Urtica hyperborea. We employed UPLC YMC-Triart C18(2. 1 mm×100 mm,1. 9 μm) column to UPLC analysis with acetonitrile-water(containing 0. 4% formic acid) in gradient as mobile phase. The flow rate was 0. 3 m L·min-1 gradient elution and column temperature was 30℃; the injection volume was 4 μL. ESI ion source was used to ensure the data collected in anegative ion mode. The chemical components of U. hyperborea were identified through retention time,exact relative molecular mass,cleavage fragments of MS/MS and reported data.The results indicated that a total of 31 compounds were identified,including 8 flavonoids,14 phenolic compounds,8 phenylpropanoids(4 coumarins and 4 lignans),and 1 steroidal compound,13 of which were confirmed by comparison. The UPLC-ESI-Q-TOF-MS/MS method could rapid identify the chemical components of U. hyperborea. The above compounds were discovered in U. hyperborea for the first time,which could provide theoretical foundation for further research on the basis of the pharmacodynamics of U. hyperborea.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Flavonoids ; Lignans ; Phenols ; Phytochemicals ; analysis ; Plant Extracts ; analysis ; Tandem Mass Spectrometry ; Urticaceae ; chemistry