A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved significantly after solidified by oral fast dissolving film technology without pharmacodynamic properties changed significantly.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Cell Line, Tumor ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Humans ; Male ; Mice ; Neoplasms ; drug therapy ; Phospholipids ; chemistry ; Solubility ; Triterpenes ; administration & dosage ; chemistry

OBJECTIVETo investigate the significance of Rac subfamily members in the gastrointestinal carcinogenesis and progression.

METHODSThe mRNA expression of Rac1, Rac2 and Rac3 in 12 kinds of gastrointestinal cancer cell lines was examined by semi-quantitative RT-PCR. The activities of Rac1 protein in 5 kinds of gastric cancer cell lines were tested by pull-down assay.

RESULTSCompared with the normal gastric mucosa and intestinal epithelial cell line, the mRNA expression of Rac1 and Rac3 was up-regulated in most of gastrointestinal cancer cell lines. The activities of Rac1 protein increased markedly in gastric cancer cell lines.

CONCLUSIONThe increased mRNA expression of Rac1 and Rac3 in gastrointestinal cancer cell lines and the abnormal activation of Rac1 protein in gastric cancer cell lines might be correlated with the carcinogenesis of gastrointestinal cancer.

Cell Line, Tumor ; Gastrointestinal Neoplasms ; metabolism ; Humans ; RNA, Messenger ; analysis ; Reverse Transcriptase Polymerase Chain Reaction ; rac GTP-Binding Proteins ; genetics ; rac1 GTP-Binding Protein ; analysis ; genetics

Objective To investigate the prevalence change of drinking water type of endemic fluorosis and the effect of control measures implemented in Huangyuan county of Qinghai province. Methods In 2009, all the endemic fluorosis villages in Huangyuan county were divided into two degrees, light and medium, according to the water fluorosis content before implementing the improving water project, 1 to 2 villages were selected from each degree village, respectively,as monitoring sites, and a total of 3 villages were selected. Source water and tap water samples were collected from each village and water fluoride concentration was determined. Dental fluorosis of all children aged 8 to 12 of monitoring villages was examined, and urine samples were collected by age group of children for determination of urinary fluoride. Clinical skeletal fluorosis of adults over 16 years of age was examined, and 20 copies of adults urine samples were collected to determine urinary fluoride. One village was selected in the 3 villages monitored to conduct X-rays examination of skeletal fluorosis. Water fluoride was tested in accordance with the "Non-metallic Targets Test Methods for Drinking Water" (GB/T 5750.6-2006); urinary fluoride was tested by fluoride ion-selective electrode method (WS/T 89-1996); dental fluorosis was diagnosed using Dean method;adult skeletal fluorosis was diagnosed by "Clinical Diagnostic Criteria for Endemic Skeletal Fluorosis"(WS 192-2008). Results Twelve water samples were assayed, water fluoride was (0.35 ± 0.43) mg/L. The detectable rate of dental fluorosis of 122 children aged 8-12 was 34.43%(42/122) and the geometric mean urinary fluoride was 0.89 mg/L of the 96 children. Of the 834 adults aged 16 and over, clinical detection of skeletal fluorosis was 47.72% (398/836) and geometric mean urinary fluoride was 1.10 mg/L of the 65 cases of adult urine samples assayed, detection rate of X-rays was 31.4% (11/35) in Gangou village of the 35 adults examined.Conclusions In Huangyuan county, water fluoride of the 3 surveyed villages are normal but the endemic fluorosis is still serious. It should strengthen monitoring and analyze the causes and improve prevention measures.

Objective To evaluate the pharmacodynamics of saikosapo-nin d ( SSd) in the treatment of hepatoma model rat.Methods Sixty SD rats with succeed modeling were randomly divided into model group ( n=20 ) , experimental group ( n=20 ) and control group ( n=20 ) , 20 SD rats without modeling were conducted to placebo group.The experi-mental group was treated with SSd 10 mg? kg -1 once a day, the control group was treated with thalidomide 200 mg? kg -1 once a day, the place-bo group and model group were treated with 0.9% NaCI 2 mL once a day.Liver function index were compared by Biochemical analysis me-thod, proliferating cell nuclear antigen ( PCNA) and MKI-67 gene en-codes nuclear protein(Ki-67) were compared by immunohistochemistry after 6 weeks.Results Compared with the model group, liver function index as well as the expression of PCNA and Ki-67 of the control group and the experiment group were lower (P<0.05).Compared with the control group, liver function index with expression of PCNA and Ki-67 of the experiment group were lower ( P<0.05).Pathological display:the pathological sections of the liver in the placebo group showed that the structure of the normal liver was complete, the liver cells were neat, the liver cells were arranged regularly, and the nu-cleus was clear.The model group showed that the tumor foci were in the shape of the necrosis, and the structure of the normal liver was destroyed, and the white nodules were the liver cancer cells.A small amount of low malignant degree, focal necrosis of cancer cells and fewer mitoses could be observed in control group, a small amount of blood and rare mitotic figures could be seen in the experiment group.Conclusion SSd can significantly improve liver function, repair the damage of liver cells, and reduce protein expression of PCNA and Ki-67 in model rats.

OBJECTIVETo confirm whether human MHC class I chain-related A (MICA) induces the amplification of V delta 1 gamma delta tumor-infiltrating lymphocytes (TILs) in vitro and to identify the cytotoxicity of MICA-reactive V delta 1 gamma delta TILs towards epithelial tumor cells.

METHODSMICA protein was prokaryoticly expressed and purified by molecular cloning technology. The purified recombined MICA (rMICA) was used to induce V delta 1 gamma delta T cells from tumor tissues in vitro and the cytotoxicity of these V delta 1 gamma delta TILs were tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT).

RESULTSThe rMICA was expressed in prokaryocyte with pET30 as a vector. The immobilized rMICA protein could markedly induce the amplification of V delta 1 gamma delta T cells from tumor tissue in vitro. These V delta 1 gamma delta T cells showed strong cytolytic activities towards tumor cell lines expressing MICA.

CONCLUSIONThe MICA-reactive V delta 1 gamma delta T cell may be a candidate for adoptive cellular therapy of tumors.

Adult ; Aged ; Female ; HeLa Cells ; pathology ; Histocompatibility Antigens Class I ; biosynthesis ; genetics ; Humans ; Immunotherapy, Adoptive ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Membrane Proteins ; biosynthesis ; genetics ; Middle Aged ; Ovarian Neoplasms ; immunology ; Receptors, Antigen, T-Cell, gamma-delta ; immunology ; Recombinant Proteins ; biosynthesis ; genetics ; T-Lymphocytes, Cytotoxic

Leupaxin (LPXN) is a new member of the Paxillin superfamily, mainly located in focal adhesion plaques, involved in the transduction of multiple signaling pathways, and regulating the proliferation, adhesion and migration of tumor cells. In prostate cancer cells, LPXN is not only involved in the integrin signaling transduction pathway, regulating the proliferation, adhesion and migration of prostate cancer cells, but is also a new androgen receptor (AR) coactivator, regulating the transcription of nuclear AR effect genes, participating in AR signal transduction, and regulating the differentiation and invasion of prostate cancer cells. This review focuses on the molecular structure, special roles and molecular mechanisms of LPXN involved in prostatic carcinoma metastasis.
Cell Adhesion Molecules ; genetics ; metabolism ; Humans ; Male ; Neoplasm Metastasis ; Phosphoproteins ; genetics ; metabolism ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; Receptors, Androgen ; metabolism ; Signal Transduction

To study the effects of Qingdai compound on proliferation and apoptosis of K562 cells, as well as the expression of bcr/abl and JWA mRNA, K562 cells were treated in culture with different concentrations of Qingdai compound (2.5, 5, 7.5, 10 and 20 mg/ml) and harvested at 24 hours. Then morphological changes were observed by light microscopy (LM); expressions of bcr/abl and JWA were detected with semi-quantitative RT-PCR. The results showed that morphological changes were observed as the increment of the Qingdai compound concentration. Inhibition effects on proliferation and apoptosis in K562 cells were seen. A concentration-dependent decreases were found in bcr-abl and JWA mRNA expression of K562 cells. Qingdai compound partially inhibited proliferation and induced apoptosis of K562 cells. Expressions of both bcr/abl and JWA, which took part in cell proliferation and apoptosis, were down-regulated in a dose dependent manner. In conclusion, Qingdai compound can partially inhibit the expressions of bcr/abl and JWA genes in K562 cells, and the clinical effect of Qingdai compound on CML may be associated with apoptosis of leukemic cells.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Fusion Proteins, bcr-abl ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Heat-Shock Proteins ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; K562 Cells ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Suppressor of cytokine signaling (SOCS) is a new family of proteins produced in cells. It may play an important role in classic negative feedback loop to regulate cytokine signal transduction. SOCS-1 was observed and confirmed firstly. Expression of SOCS-1 can inhibit cytokine signal transduction of some cytokines, such as IL-6, LIF, OSM, INF-gamma, GH, and so on, many immune responses are regulated by them in vivo. Abnormal expression of SOCS-1 is closely related to some human diseases. It plays an important role in the development of leukemia, rheumatoid arthritis, liver cirrhosis and liver cancer. In this review, the advances of research on the relationship between SOCS-1 and cytokine, and its correlation with some diseases were summarized.
DNA Methylation ; Humans ; Interleukin-6 ; biosynthesis ; Intracellular Signaling Peptides and Proteins ; Leukemia ; etiology ; genetics ; Leukemia Inhibitory Factor ; biosynthesis ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling Proteins ; biosynthesis ; genetics ; physiology

OBJECTIVETo analyse the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria (DSH).

METHODSA pedigree of DSH was investigated. Mutation scanning was carried out by PCR and direct sequencing. ADAR gene of 50 normal people was also sequenced as control. Through CBMdisc and PubMed, the mutations of ADAR gene were summarized.

RESULTSA novel mutation of c.2447G > A was found in all patients with DSH, but was not found in normal individuals in this DSH family and 50 unrelated controls. There were 64 mutations in ADAR gene.

CONCLUSIONA deletion mutation (c.2447G > A) in the ADAR gene has been detected in this DSH family, which is probably one of the molecular bases of the pathogenesis of the disease. Author have summarized a total of 64 mutations in the ADAR gene by previous reports and speculate that the mutation hotspots of ADAR gene might be located in the tRNA-specific and double-stranded RNA adenosine deaminase (ADEAMc) domain.

Adenosine Deaminase ; genetics ; Adult ; Base Sequence ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Pigmentation Disorders ; genetics ; Polymerase Chain Reaction ; RNA-Binding Proteins ; Skin Diseases, Genetic ; genetics

In order to investigate the suppressor of cytokine signaling-1 (SOCS-1) expression in peripheral blood mononuclear cells (PBMNC) of patients with acute and chronic myeloid leukemia and analyze its clinical significance, RT-PCR method was used for detecting SOCS-1 mRNA expression in PBMNC of 50 newly diagnosed patients. The result showed that positive expressions of SOCS-1 were observed in 4 of 25 patients with AML (16.00%), in 11 of 25 patients with CML (44.00%) and none in 10 normal controls. The differences between patients with AML and normal controls, and between patients with CML and normal controls were statistically significant. In CML group, 2 out of 12 cases with non-progression (chronic phase), 9 of 13 cases with progression showed the positive expression, the difference between two subgroups was statistically significant. Those CML patients with SOCS-1 mRNA expression had poor response to IFN-alpha. When they transformed into accelerated phase, SOCS-1 mRNA expression was more persistently and frequently observed, and no response to IFN-alpha was observed. Most of them had very poor prognosis. It is concluded that the SOCS-1 mRNA can be detected in the PBMNC of the patients with acute and chronic myeloid leukemia. The SOCS-1 mRNA expression in the patients with CML is higher than that in patients with AML, and it is higher in accelerated phase and blast crisis significantly. This phenomenon is highly related to the reaction of IFN-alpha and prognosis.
Humans ; Interferon-alpha ; metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling Proteins ; biosynthesis ; genetics