This study aimed to investigate the effects of concentration, intestinal section and borneol on the intestinal absorption of salvianolic acids. The experiment not only studied the intestinal absorption properties of three concentrations of rosmarinic acid, salvianolic acid B and salvianolic acid A at duodenum, jejunum and ileum, but also of salvianolic acids compatible with borneol at different concentrations using single-pass intestinal perfusion model in rat with phenol red as the marker. The results showed that salvianolic acids was stable under weak-acid condition and affected by metabolism enzyme; The Peff and Ka significantly different among three concentrations of rosmarinic acid and salvianolic acid B, whose intestinal absorption were saturated in high concentration, suggesting that the transport mechanisms of rosmarinic acid and salvianolic acid B were similar to active transport or facilitated diffusion; However, there was inconspicuousness in the Peff and Ka of salvianolic acid A at different concentrations, whose absorption was not saturated in high concentration, indicating that the transport mechanisms of salvianolic acid A was passive diffusion; The Peff and Ka in the ileum obviously higher than those in the duodenum and jejunum, namely the ileum was the best absorption section; When concentration of borneol increased, the enhancing effect of intestinal absorption of salvianolic acids increased, but significantly decreased when borneol increased to some degree. The enhancing effect of medium borneol concentration was the optimum. This implied that borneol can enhance the intestinal absorption of salvianolic acids, and the capacity of enhancing effect was influenced by the concentration of borneol.
Animals ; Benzofurans ; isolation & purification ; pharmacokinetics ; Bornanes ; administration & dosage ; pharmacokinetics ; pharmacology ; Caffeic Acids ; isolation & purification ; pharmacokinetics ; Cinnamates ; isolation & purification ; pharmacokinetics ; Depsides ; isolation & purification ; pharmacokinetics ; Dose-Response Relationship, Drug ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Lactates ; isolation & purification ; pharmacokinetics ; Male ; Perfusion ; methods ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.

The aim of the study is to investigate rat intestinal absorption behavior of three main active components, schisandrol A, schisandrin A and schisandrin B in Schisandra chinensis Baill extracts in intestine of rats. With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and the concentrations of three main active components in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection. The results showed that the absorption rate constant (Ka) and effective permeability values (Peff) of three main active components in Schisandra chinensis Baill extracts had significant difference (P < 0.05) at different concentrations of perfusion solution, the Ka and Peff first increased and then decreased with the increase of drug concentration, the middle concentration was higher than those of the other two concentrations. The saturate absorption phenomena were observed, and it suggested that the transport mechanisms of three main active components in vivo were similar to active transport or facilitated diffusion. Three active components can be well absorbed in all of the intestinal segments, while duodenum is the best absorption region. The Ka and Peff of three active components in jejunum and ileum had no significant difference (P > 0.05). The absorption of the three active components displayed significant difference (P < 0.05) at different intestinal segments of rats. Schisandrin A had the best absorption in duodenum. The Ka and Peff among three active components were sequenced as follows: schisandrin A > schisandrin B > schisandrol A in other intestinal segments, and there is significant difference (P < 0.05) between them.
Animals ; Chromatography, High Pressure Liquid ; Colon ; metabolism ; Cyclooctanes ; administration & dosage ; isolation & purification ; pharmacokinetics ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Duodenum ; metabolism ; Fruit ; chemistry ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Lignans ; administration & dosage ; isolation & purification ; pharmacokinetics ; Male ; Perfusion ; Permeability ; Plants, Medicinal ; chemistry ; Polycyclic Compounds ; administration & dosage ; isolation & purification ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Schisandra ; chemistry

Adult ; Female ; Hepatitis B, Chronic ; complications ; physiopathology ; Humans ; Liver ; physiopathology ; Liver Function Tests ; Male ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; complications ; physiopathology

Antigens, Surface ; analysis ; Antiretroviral Therapy, Highly Active ; CD28 Antigens ; analysis ; CD56 Antigen ; analysis ; HIV Infections ; drug therapy ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; analysis ; NK Cell Lectin-Like Receptor Subfamily B ; NK Cell Lectin-Like Receptor Subfamily D ; analysis ; Receptors, Immunologic ; analysis ; Receptors, KIR

OBJECTIVETo determine the seasonal prevalence of genotype-IV hepatitis E virus (HEV) in swine herds in Eastern China and explore the phylogenetic relationship between swine HEV and human HEV in the situation that zoonotic features of HEV had been confirmed.

METHODSFrom September 2007 to June 2008, a total of 1200 swine bile specimens were collected from three slaughter houses located in Zhejiang, Anhui and Jiangsu, the Eastern China, and detected for HEV RNA by using nested RT-PCR. The positive PCR products were sequenced. Then the swine HEV were phylogenetically determined with human HEV isolated in Eastern China.

RESULTSThe positive rate for HEV RNA in swine herds was 4.5% totally. Significant differences of HEV detection were not observed among seasonal pattern (Sep - Oct: 6%, Dec - Jan: 4.33%, Mar - Apr: 4.33%, May - Jun: 3.33%) but in geographic distribution (Jiangsu: 6%, Anhui: 5%, Zhejiang: 2.5%). Regardless of isolation from different areas,swine and human genotype-IV HEV shared a high similarity. Phylogenetically, there were 80% - 100% and 96% - 100% identities within swine genotype-lV HEV at the nucleotide and amino acid levels respectively. Between swine HEV and human HEV, there were also similarities of 76% -99% and 95% - 100%. It was noted that some human and swine isolates were clustered with bootstrap values of > 90%.

CONCLUSIONGenotype-IV HEV is widely prevalent in swine herds in Eastern China and original common ancestor of evolution and transmission was implied. The sustaining prevalence within swine herds should have a probable influence on the epidemic situation of hepatitis E in human beings.

Animals ; China ; epidemiology ; Genotype ; Geography ; Hepatitis E ; epidemiology ; Hepatitis E virus ; classification ; genetics ; isolation & purification ; Humans ; Phylogeny ; Prevalence ; Seasons ; Sequence Homology, Nucleic Acid ; Swine ; Swine Diseases ; epidemiology ; genetics ; virology

OBJECTIVETo study the polymorphisms and secondary structure of human immunodeficiency virus (HIV-1) tat exon 1 among subtype B' and B'/C HIV-1 infected people in China and to explore the relationship between the polymorphism of tat exon 1 and the disease progression.

METHODS8 subtype B' and 5 B'/C HIV-1 infected patients with slow disease progression were selected from Liaoning, Jilin and Yunnan province. 26 subtype B' and 9 B'/C HIV-1 infected patients with similar sex, age but with typical disease progression were selected. Provirus was extracted from the whole blood. The gene sequences of the Tat exon 1 were amplified by nest-polymerase chain reaction (nest-PCR). Products were purified and sequenced directly. The sequences were aligned, translated, amino acid substitution were analyzed and secondary structures were predicted.

RESULTSMany amino acid substitution could be found in the exon 1 of Tat in HIV-1 subtype B' and B'/C recombinant strain infected persons with different disease progression except A58T,none of them showed definitely relationship with HIV viral load and disease progression. 23N, 31S, 32Y and 46F were subtype-specific substitutions. No characteristic secondary structure of exon 1 of Tat was found.

CONCLUSIONSome of the mutations of tat exon 1 might be related to HIV viral load and disease progression. However, there was no relationship found between the secondary structure of Tat protein and the disease progression.

Acquired Immunodeficiency Syndrome ; genetics ; pathology ; Amino Acid Substitution ; Disease Progression ; Exons ; genetics ; Genes, tat ; genetics ; HIV Infections ; genetics ; pathology ; Human Immunodeficiency Virus Proteins ; genetics ; Humans ; Polymorphism, Genetic ; Viral Load

Objective To observe the clinical efficacy and safety of acetylcysteine effervescent tablets in the treatment of chronic obstructive pulmonary disease (COPD).Methods One hundred and seventy-four patients with COPD were randomly divided into control and treatment groups with 87 cases per group.Control group was treated with bronchial diastolic,anticholinergic,β2 receptor agonist and glucocorticoid,and so on.Treatment group was given acetylcysteine effervescent tablets 600 mg per time,bid,orally,on the basis of control group.Tow groups were treated for 4 weeks.The clinical efficacy,lung function,the levels of interleukin-4 (IL-4) and IL-6 in serum and induced sputum,serum oxidative stress indexes and adverse drug reactions were compared between two groups.Results After treatment,the total effective rates of treatment and control groups were 91.95％ (80 cases / 87 cases) and 77.01％ (67 cases / 87 cases) with significant difference (P ＜ 0.05).After treatment,the main indexes in treatment and control groups were compared:the forced expiratory volume in one second were (1.89 ± 0.21) and (1.47 ± 0.18) L,forced vital capacity were(2.45±0.17) and (2.21±0.12)L,serum IL-4 were (0.93±0.07) and (1.17±0.16)ng·L-1,serum IL-6were (18.44 ±2.32) and (33.98 ±3.58)ng · L-1,induced sputum IL-4 were (1.61 ±0.22) and (2.15 ±0.27)ng · L-1,induced sputum IL-6 were (65.85 ± 11.34) and (82.18 ± 17.74)ng · L-1,serum malondialdehyde were (633.23 ± 76.85) and (715.46 ± 84.36) μmol · mL-1,reactive oxygen species were (49.78±6.35) and (62.77 ± 8.49)U · mL-1,superoxide dismutase were (261.15 ± 25.47) and (218.83 ±24.34)U · mL-1,glutathione peroxidase were (29.95 ±3.07) and (20.74 ±2.16) μmol · L-1,with significant differences (all P ＜ 0.05).The adverse drug reactions of two groups were stomach upset,insomnia,headache and hand tremor,and there was no significant difference on the incidence of adverse reactions in treatment and control groups (10.35％ vs 6.90％,P ＞ 0.05).Conclusion Acetylcysteine effervescent tablets have a definitive clinical efficacy in the treatment of COPD,which can improve the lung functions,reduce the levels of IL-4 and IL-6 in serum and induced sputum,inhibit oxidative stress response,without increasing the incidence of adverse drug reactions.

Tanshinones are abietane-type norditerpenoid quinones that make up the main bioactive ingredients of traditional Chinese medicine Salvia miltiorrhiza. Cytochrome CYP450 plays an important role in the post-structural modification of tanshinone biosynthesis pathway. Long non-coding RNA( lncRNA) have been defined as transcripts longer than 200 nucleotides,which have been functionally characterized in regulating the growth and development,secondary metabolism and stress of medicinal plants. In this study,we perform a comprehensive identification of lncRNAs in response to tanshinone metabolism induced by yeast extract( YE) and Ag~+ S. miltiorrhiza hairy roots. Deep RNA sequencing was used to identify a set of different 8 942 lncRNAs,of which 6 755 were intergenic lncRNAs. We predicted a total of 1 115 814 lncRNA-coding gene pairs,including 122 lncRNA-coding gene as cis pairs. The correlation analysis between lncRNA and CYP450 related to tanshinone biosynthesis was carried out and a total of 16 249 lncRNA-CYP450 target gene pairs were identified. Further analysis with functional known CYP76 AH1,CYP76 AH3 and CYP76 AK1 involved in tanshinone biosynthesis,we also identified a set of 216 target genes. These candidate genes will be the important target in the downstream regulation mechanism analysis of the tanshinone biosynthesis pathway.
Cytochrome P-450 Enzyme System ; genetics ; Diterpenes, Abietane ; biosynthesis ; Gene Expression Regulation, Plant ; Plant Roots ; RNA, Long Noncoding ; genetics ; RNA, Plant ; genetics ; Salvia miltiorrhiza ; genetics

BACKGROUNDAndrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.

METHODSCell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.

RESULTSAndrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.

CONCLUSIONSAndrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

Apoptosis ; drug effects ; Caspase 3 ; analysis ; genetics ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein ; analysis ; genetics