Osmotically controlled oral drug delivery systems (OCODDSs) utilize osmotic pressure for controlled delivery of active agents. The release of drugs from osmotic systems is governed by various formulations and processing factors such as solubility and pressure of the core components, properties of the semi-permeable membrane. In the present review, the references on OCODDSs have systematically been summarized in the following aspects: prescription design, industrial processing and equipments, methods for quality evaluation, and general situation of application. Prospect of applying the osmotic-pump technology into Chinese patent drugs is also discussed.
Administration, Oral ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; administration & dosage ; Osmotic Pressure

OBJECTIVETo study the effects of Angelica sinensis Polysaccharides (ASP) on the hepatic drug metabolism enzymes activities in normal mice and those prednisolone (PSL)-induced liver injury.

METHODThe activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method.

RESULTASP increased the activities of glutathione S-transferase in liver microsomes and mitochondria. The cytochrome P450 content, NADPH-cytochrome c reductase, aminopyrine N-demethylase, and aniline hydroxylase activities in liver microsomes were also increased. PSL significantly increased serum ALT levels, and decreased the liver mitochondrial glutathione content. At the same time, other enzymes activities were all increased. When mice were treated with ASP 2.0 g.kg-1, the PSL-induced changes on cytochrome P450 enzymes, glutathione S-transferase, and GSH content were restored.

CONCLUSIONASP can modulate the activities of drug metabolism enzymes.

Aminopyrine N-Demethylase ; metabolism ; Angelica sinensis ; chemistry ; Aniline Hydroxylase ; metabolism ; Animals ; Chemical and Drug Induced Liver Injury ; enzymology ; etiology ; Cytochrome P-450 Enzyme System ; metabolism ; Glutathione Transferase ; metabolism ; Male ; Mice ; Microsomes, Liver ; enzymology ; Mitochondria, Liver ; enzymology ; NADPH-Ferrihemoprotein Reductase ; metabolism ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Prednisolone

A full-length cDNA encoding a MYB-related regulatory gene was isolated from a cDNA library prepared from mRNAs of the red line callus of S. medusa by TD-PCR. The cDNA, designated SmP, is 969 nucleotides long and has an open reading frame of 771 bp with a deduced amino acid sequence of 256 residues. The putative protein of SmP has two typical conversed R2R3-Myb DNA-binding domains in N-terminal and displays a rather high degree of similarity to OsMYB from rice and LBMI from tobacco, showing 73% and 70% identity within the DNA-binding domains. However, the C-terminal domain of the SmP protein does not show obvious similarity to any other known protein sequence. It is rich in hydrophilic amino acids, especially in serine residues (18.38%), partly organized in homopolymeric stretches, a feature often found in activation domain of transcription factors.
Amino Acid Sequence ; Cloning, Molecular ; Molecular Sequence Data ; Phylogeny ; Plant Proteins ; chemistry ; classification ; genetics ; metabolism ; Polymerase Chain Reaction ; Saussurea ; classification ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Transcription Factors ; chemistry ; genetics ; metabolism

OBJECTIVETo investigate the expressions of TopI gene in small cell lung cancer cell line H446, and explore the influence of TopI on the chemosensitivity of the cell line to topotecan (TPT).

METHODSWestern blot was performed to detect the TopI expression in H446 cells. Lipofectamine 2000 was used for the transient transfection of H446 cells by siRNA, and the transfection efficacy was detected. TopI mRNA was analyzed by quantitative RT-PCR and TopI protein was detected by Western blot to selected effective siRNA. The drug-sensitivity to topotecan (TPT) was evaluated by MTT assay.

RESULTSTopI gene was expressed in H446 cells. Lipofectamine 2000 mediated the siRNA effectively (88.67%). Compared with its parental cells, RT-PCR results showed that TopI mRNAs in transfected cells were reduced by (95.7 +/- 1.6)%, (90.8 +/- 1.6)%, (96.1 +/- 2.7)% and (96.3 +/- 1.8)%, respectively, and decreased significantly at protein level. By MTT assay, the inhibition rate of TPT to H446 cells transfected by siRNA was lower than that of control group at same concentrations (P < 0.01).

CONCLUSIONsiRNAs can silence the expression of TopI and decrease the drug-sensitivity of H446 cells to TPT.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; genetics ; metabolism ; Down-Regulation ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Small Cell Lung Carcinoma ; metabolism ; pathology ; Topotecan ; pharmacology ; Transfection

Animals ; Arterioles ; metabolism ; pathology ; Blood Pressure ; drug effects ; Chemokine CX3CL1 ; Chemokines, CX3C ; analysis ; genetics ; Chronic Disease ; Flavonoids ; pharmacology ; Hypertension, Pulmonary ; prevention & control ; Hypertrophy, Right Ventricular ; prevention & control ; Hypoxia ; complications ; metabolism ; Lung ; metabolism ; Male ; Membrane Proteins ; analysis ; genetics ; Pulmonary Artery ; metabolism ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley

Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. Conclusion The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.

The aim of the present study was to investigate the effect of tetramethylpyrazine (TMP) on the changes of respiration and expression of neuronal nitric oxide synthase (nNOS) in brainstem induced by hypoxia in the rats. Hypoxia was induced by inhalation of 8% O2-balanced N2.The electromyogram (EMG) of diaphragm was monitored to evaluate the respiratory response of the rats to hypoxia. The immunohistochemical staining technique was used to study the change of the expression of nNOS in the brainstem during hypoxia. In the rats of hypoxia group, a successive process of response, excitatory followed by inhibitory, was produced. Twenty min after hypoxia, a significant inhibition of respiration occurred, which was characterized with a marked decrease in the inspiratory duration, the respiratory frequency, and the amplitude of inspiration and a prolongation of expiratory duration (P<0.05). In the rats of pretreated with TMP, the respiratory activity was not obviously depressed (P>0.05). In the rats of hypoxia group, the level of nNOS immunoreactivity was enhanced remarkably in the lateral reticular nucleus, nucleus of trapezoid, hypoglossal nucleus and the facial nucleus compared with the control group (P<0.05). In the rats of pretreated with TMP, the nNOS level increased further in the nuclei mentioned above (P<0.05). The results obtained indicate that TMP can reverse the inhibitory effect of hypoxia on respiration in the rats and that nNOS may be involved in the respiratory protective action of TMP.
Animals ; Brain Stem ; enzymology ; physiopathology ; Female ; Hypoxia ; physiopathology ; Male ; Nitric Oxide Synthase Type I ; genetics ; metabolism ; Pyrazines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiration ; drug effects ; Respiratory Insufficiency ; prevention & control

OBJECTIVETo study the effect of Shenfu Injection (SF) on the apoptosis of prostate cancer PC-3 cells and its possible mechanism.

METHODSWe divided prostate cancer PC-3 cells into a blank control group and three experimental groups, the latter treated with SF at 50, 100, and 200 microl/ml, respectively, for 24, 48, and 72 hours. Then we determined the proliferation of the cells by MTT assay, measured their apoptosis by Annexin V/PI flow cytometry, and detected the expression of P53 mRNA by RT-qPCR.

RESULTSCompared with the blank control group, the survival rates of the prostate cancer PC-3 cells in the 50, 100, and 200 microl/ml SF groups were (93.76 +/- 2.63)%, (81.21 +/- 1.80)% and (18.01 +/- 3.84)% at 24 hours, (94.67 +/-1.11)%, (78.33 +/- 2.89)% and (10.34 +/- 1.44)% at48 hours, and (91.30 +/- 0.47)%, (36.67 +/- 1.56)% and (1.33 +/- 0.32)% at 72 hours, all significantly increased in a dose- and time-dependent manner (P < 0.05). The expression of p53 mRNA was also markedly increased in all the three experimental groups at 48 hours (P < 0. 05).

CONCLUSIONSF can inhibit the proliferation and induce the apoptosis of PC-3 cells, which may due to its upregulation of the p53 mRNA expression.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Objective To evaluate the effect of personnel activities and air purifiers on airborne microorganisms and particulate matter in bronchoscopy room.Methods According to whether there was personal activity and air purifier in the bronchoscopy room,the experiment was divided into four groups:dynamic non-purification group,dynamic purification group,static non-purification group,and static purification group,indoor air samples were collected and analyzed at five different time points (0,0.5,1,2,4 h),microorganisms in the air were collected by planktonic method,then cultured and counted,concentration of particulate matter was determined by DT-9881M laser dust particle counter,variance analysis of factorial design was used for statistical analysis.Results Colony count/concentration of airborne bacteria,fungi,total microorganisms (bacteria + fungi),PM2.5,and PM2.5-10.0 in dynamic non purification group were (113.53 ± 7.78) CFU/m3,(89.67 ± 7.17) CFU/m3,(203.20 ± 10.92) CFU/m3,(86 557.20 ±4 158.29) counts/m3,and (659.69 ± 38.91) counts/m3 respectively,in static non-purification group were (84.33 ± 3.65) CFU/m3,(65.00 ± 2.65)CFU/m3,(149.33 ± 4.98) CFU/m3,(45 812.64 ±1 279.61) counts/m3,and (189.15 ± 4.64) counts/m3 respectively,in dynamic purification group were (84.80 ±8.08) CFU/m3,(90.40 ± 5.50) CFU/m3,(175.20 ± 9.22) CFU/m3,(49 336.38 ± 2 039.16) counts/m3,and (218.36 ± 7.02) counts/m3 respectively,in static purification group were (67.80 ± 5.63) CFU/m3,(38.27 ± 3.70)CFU/m3,(106.07 ± 6.76) CFU/m3,(29 772.53 ± 2 212.93) counts/m3,and (124.80 ± 7.16) counts/m3 respectively.Colony count/concentration of airborne bacteria,total microorganisms,PM2.5,and PM2.s 10.0 in dynamic group were all higher than those in static group,non-purification group were higher than purification group(both P ＜0.05),colony count of fungi in dynamic non-purification group was higher than static non-purification group,in static purification group was lower than static non-purification group(both P＜0.05),there was no significant difference between dynamic purification group and dynamic non-purification group (P =0.936).Conclusion Personal activities can increase colony count/concentration of microorganisms and particulate matter in bronchoscopy room,air purifier can reduce the bacteria,total microbial count,and particulate matter in the air of bronchoscopy room.

Snake venom has special pharmacological activities and contains a array of small polypeptides that can antagonize integrins, therefore called disintegrins. Disintegrins can block integrin-dependent platelet aggregation, tumor growth, and tumor metastasis. A disintegrin fraction was isolated and purified from the venom of snake Gloydius brevicaudus (GBV). Its physical and chemical properties were characterized, and its biological activities were investigated. The crude venom of GBV were isolated by Superdex 75 gel filtration chromatography. The anti-platelet aggregation activity of the fractions was screened by the Born method. The fraction that shown anti-platelet activity was further purified with Sephadex G-25 gel filtration, DEAE Sepharose Fast Flow ion exchange chromatography, and Lichrospher C18 reversed-phase chromatography respectively. The purity of the active component was analyzed with SDS-PAGE (Tris-Tricine system) and high-performance liquid-phase chromatography (HPLC), with protein concentration determined by the Bradford method. The molecular weight was evaluated by the gel imaging method and mass spectrometry, and the isoelectric point was measured by disc isoelectric focusing electrophoresis. The protease activity was measured with the Rick method. The phospholipase A activity was determined by the automatic potentiometric titration method. Amino acid sequencing results were subjected to homology comparison using the BLAST program. Seven fractions (Ⅰ-Ⅶ) were isolated from GBV by gel filtration chromatography on Superdex 75 column. The fraction Ⅳ inhibited the platelet aggregation induced by ADP with molecular weight lower than 10 000 Da, suggesting a disintegrin component. A disintegrin named GBV-Ⅳ4 was purified from the fraction by Sephadex G-25 gel filtration, DEAE Sepharose Fast Flow ion-exchange and Lichrospher C18 reverse chromatography. It was homogeneous shown as a single band on SDS-polyacrylmide gel electrophoresis (SDS-PAGE, Tris-Tricine system) with molecular weight 8 746 Da as calculated by Image Master VDS system. The isoelectric point of GBV-Ⅳ4 was 6.3 by disc polyacrylamide gel electrophoresis. GBV-Ⅳ4 exhibited no detectable phospholipase A₂ (PLA₂) activity with the pH-stat technique or proteinase activity according to the method of Rick. GBV-Ⅳ4 is composed of 70 amino acids with RGD (Arg-Gly-Asp) active region and a molecular weight of 7 442 Dalton as assayed by Mass Spectrography. Characterization of GBV-Ⅳ4 is consistent with meta-chain disintegrin (70 amino acid sequence, six pairs of disulfide bond). Retrieved by Genbank, GBV-Ⅳ4 has high homology with other disintegrins. We concluded that GBV-Ⅳ4 is a novel disintegrin contained RGD. GBV-Ⅳ4 showed dose-dependent inhibition of ADP- or thrombin-induced platelet aggregation with IC₅₀ 0.339 or 0.577 μg·mL^-1 respectively. In conclusion, a new disintegrin derived from the GBV snake venom and named GBV-Ⅳ4 containing RGD tripeptide sequence could inhibit platelet aggregation.