With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

OBJECTIVETo investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease.

METHODSFifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1.

RESULTSMS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children in the control group had mRNA expression of ZO-1. There was no linear relationship between the total number of peripheral blood leukocytes and ZO-1 gene IOD (r=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001).

CONCLUSIONSZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.

Adolescent ; Child ; Child, Preschool ; DNA Methylation ; Female ; Humans ; Infant ; Lymphoma, Non-Hodgkin ; genetics ; Male ; Promoter Regions, Genetic ; Zonula Occludens-1 Protein ; genetics

OBJECTIVESTo investigate the effects of microcystins on cell cycle and expressions of c-fos and c-jun, and explore the potential carcinogenic mechanisms of Microcystins.

METHODSMicrocystic cyanobacteria extraction (MCE) purified by Sep-Pak C(18) cartridge was added into the media and co-incubated with SHE cell for various periods. Immunohistochemistry assay was applied to detect the expressions of c-fos and c-jun at 1, 3, 6 hr time point, and cell cycle at 6, 12, 24 hr point were analyzed by flow cytometry respectively.

RESULTSSustained up-regulated expression of c-fos and c-jun were induced by MCE during the experimental period, and 5 - 6 folds increased expression were observed at 6 hour point after treatment. As much as 44.8 per cent of cells were induced to entry S-phase from resting G(0)/G(1).

CONCLUSIONUp-regulating the expression of transcript factor such as c-fos and c-jun thus to induce cell abnormal proliferation may be the potential carcinogenic mechanisms of microcystins.

Animals ; Carcinogens ; toxicity ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cells, Cultured ; Cricetinae ; Gene Expression ; drug effects ; Microcystins ; Peptides, Cyclic ; toxicity ; Proto-Oncogene Proteins c-fos ; biosynthesis ; Proto-Oncogene Proteins c-jun ; biosynthesis

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Dendritic Cell Sarcoma, Follicular ; metabolism ; pathology ; Dendritic Cell Sarcoma, Interdigitating ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Granuloma ; metabolism ; pathology ; surgery ; Head and Neck Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Leukocyte Common Antigens ; metabolism ; Lymph Nodes ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Receptors, Cell Surface ; metabolism ; S100 Proteins ; metabolism ; Tonsillar Neoplasms ; metabolism ; pathology ; secondary

OBJECTIVETo determine whether lactic acid bacteria as probiotics is efficacious in the primary prevention of infantile eczema or atopic eczema.

METHODSFor this meta analysis of randomized controlled trials (RCT) describing the efficacy of probiotics in infants with eczema or atopic eczema at ages of ≤2 years, a comprehensive search in the databases was performed up to January 2010. Three reviewers independently evaluated the studies for methodological qualities. RevMan 5.0.2 software was used for meta analysis.

RESULTSTwelve RCTs on the preventive effects of lactic acid bacteria as probiotics on infantile eczema were included, and 7 of the 12 RCTs reported the preventive effect of lactic acid bacteria on atopic eczema. The meta analysis showed that there was an overall significant reduction in infantile eczema and atopic eczema favoring lactic acid bacteria compared with placebo. The relative risk (RR) ratios for eczema and atopic eczema were 0.80 (95%CI: 0.70-0.90; P<0.01) and 0.78 (95%CI: 0.64-0.97; P<0.01), respectively. Lactic acid bacteria combined with other probiotics decreased significantly the incidence of eczema, with a RR ratio of 0.79 (95%CI: 0.68-0.93; P<0.01). The use of lactic acid bacteria alone did not result in a reduction in the incidence of eczema, with a RR ratio of 0.85 (95%CI: 0.69-1.05; P>0.05).

CONCLUSIONSThe data from this meta analysis suggest that lactic acid probiotics combined with other probiotics play a role in the prevention of infantile eczema. There is insufficient evidence to recommend single use of lactic acid bacteria for prevention of eczema. Further studies are required to determine whether the findings are reproducible.

Child ; Child, Preschool ; Dermatitis, Atopic ; prevention & control ; Humans ; Lactobacillus ; Lactococcus ; Probiotics ; therapeutic use ; Randomized Controlled Trials as Topic ; Streptococcus thermophilus

Antigens, Surface ; blood ; Diagnosis, Differential ; Glutamate Carboxypeptidase II ; blood ; Humans ; Male ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; pathology ; Prostatic Neoplasms ; etiology ; metabolism ; pathology ; Racemases and Epimerases ; analysis

Adult ; Diagnosis, Differential ; Foot Diseases ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Male ; Myxosarcoma ; metabolism ; pathology ; surgery ; Neoplasms, Muscle Tissue ; pathology ; Soft Tissue Neoplasms ; metabolism ; pathology ; surgery ; Tenosynovitis ; pathology ; Vimentin ; metabolism

12E7 Antigen ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Diagnosis, Differential ; Fibrosarcoma ; metabolism ; pathology ; Heart Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Humans ; Male ; Mesothelioma ; genetics ; metabolism ; pathology ; Middle Aged ; Mucin-1 ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Pericardiectomy ; Pericardium ; pathology ; Sarcoma ; metabolism ; pathology ; Sarcoma, Synovial ; genetics ; metabolism ; pathology ; surgery ; Translocation, Genetic ; Vimentin ; metabolism

OBJECTIVEBy studying the process of reverse osmosis system for traditional Chinese medicine materials physicochemical parameters affecting the osmotic pressure of its relevance, new compound system reverse osmosis process design methods were explored.

METHODThree concentrations materials for high, middle and low were dubbed with Sini decoction as a model drug, and pretreated by 50 thousand relative molecular weight cut-off ultrafiltration membrane. The viscosity, turbidity, conductivity, salinity, TDS, pH value and osmotic pressure of each sample were determined after the reverse osmosis to study the physical and chemical parameters between their respective correlations with the osmotic pressure, and characterized by HPLC chromatograms showing changes before and after the main chemical composition of samples of reverse osmosis.

RESULTConductivity-osmotic pressure, salinity-osmotic pressure of the linear correlation coefficient, TDS-osmotic pressure between the three sets of parameters were 0.963 8, 0.932 7, 0.973 7, respectively. Reverse osmosis concentrate and its characteristic spectrum ultrafiltrate HPLC similarity were up to 0. 968 or more, except the low concentrations.

CONCLUSIONThere is a significant correlation between the three physicochemical parameters (conductivity, salinity, TDS) and osmotic pressure of each sample system, and there is also significant linear correlation between salinity, conductivity, TDS. The original chemical composition of Sini decoction material concentrate was completely remained after the process of reverse osmosis.

Chemical Phenomena ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Molecular Weight ; Osmotic Pressure ; Surface Properties ; Viscosity

OBJECTIVETo investigate the time trends and age-related characteristics of mortality and disease burden for cardiocerebrovascular diseases (CVD) in Hunan, China during three periods (1973-1975, 1990-1992 and 2004-2005).

METHODSThe cardiocerebrovascular death data of Hunan residents were collected by three national retrospective sample surveys of death. Cause-specific mortality, proportion, years of potential life lost (YPLL) and associated indicators were identified in the population of Hunan in above mentioned three periods. Time trends of age-specific mortality rate were assessed by fitting curvilinear regression lines and the increase rates of mortality with age were analyzed in each period.

RESULTSThe standard all-cause mortality of residents in Hunan decreased (chi2 = 189.947, P < 0.001, chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) while the standard mortality for CVD increased (chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) from 1973 to 2005. The age-specific mortality rate for CVD increased with age in all three periods, especially for citizens older than 60 years. There were age stages in each period in which the mortality increase rate was the fastest (10-14 and 15-19 years old in 1973-1975; 10-14, 15-19 and over 80 years old in 1990-1992; 15-19 and over 80 years old in 2004-2005). Exponential regression function (y = b0e(b1x)) can be used for the proper description of age-specific mortality change. The ratio of YPLL for CVD in all death causes showed increase trend (chi2 = 275,630.407, P < 0.001). YPLL rate (YPLLs per 1000) in 1973-1975 was higher than those in 1990-1992 and 2004-2005. YPLL rate was positively correlated with mortality in all periods.

CONCLUSIONSThe mortality for CVD increased with time and aging. People older than 60 years were threatened by CVD mostly. Mortality trend analysis also found higher CVD deaths in people age 15-19 in Hunan residents.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cardiovascular Diseases ; epidemiology ; mortality ; Cause of Death ; Cerebrovascular Disorders ; epidemiology ; mortality ; Child ; Child, Preschool ; China ; epidemiology ; Humans ; Infant ; Life Tables ; Middle Aged ; Survival Rate ; trends ; Time Factors