This study was to investigate the permeability and absorbability of capsaicin cubosome across abdominal skin of the SD rats in vitro. Diffusion of capsaicin cubosome and cream was performed with the modified Franz diffusion cell technique. The capsaicin cubosome showed no enhancement of skin permeation within 24 hours. However, the deposition amounts of capsaicin in the rat skin in the cubosome group was markedly higher than those in the commercial cream group (P < 0.01). Cubosome showed excellent characetristic of skin-targed which could be a good carrier for the local transdermal drug delivery system.
Administration, Cutaneous ; Animals ; Capsaicin ; administration & dosage ; chemistry ; Kinetics ; Male ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption

Objective To observe effects of electro-acupuncture (EA) on the expression of apoptosis related protein B-cell lymphoma/leukemia gene 2 (Bcl-2) and Bcl-associated protein X (Bax) in the hippoeampal CA1 region of rats with cerebral infarction,and on their behavior. MethodsAn animal model of cerebral ischemia was established by right side middle cerebral artery occlusion using thread in 48 male,adult Wistar rats,who were then randomly divided equally into an EA group and a control group.Both groups were sub-divided into 1 week,2 weeks and 3 weeks subgroups.The EA group began receiving EA 24h after the occlusion,applied at the Baihui (DU20) and Dazhui (BU14) points,once daily,for one,two or three weeks.The control group was reared conventionally and was not given any special treatment.The rats'learning and memory,motion and neural function were evaluated.The expression of Bcl-2 and Bax in the CA1 region of the hippocampus on the infarcted side and changes of apoptosis indexes were detected using immunohistochemical techniques.ResultsThe learning,memory,motion and neural function of the EA group rats were better on average than those of the control group at all observation time points.The expression of Bcl-2 protein increased along with reduced expression of Bax protein in the EA group significantly more than among the controls.TUNEL positive cells in the CA1 region of the hippocampus were reduced significantly in the EA group compared with the control group.ConclusionsBehavioral ability after cerebral infarction can be improved by EA at the Baihui (DU20) and Dazhui (BU14) points.EA can up-regulate the expression of Bcl-2 and down-regulate the expression of Bax and reduce TUNEL positive cells in the CA1 region of the hippocampus after cerebral infarction,which might be the mechanism of its neuroprotection.

To study the inhibitory effect of RNA interference (RNAi) on MMP-9 gene expression in THP-1 cell line.To investigate the application of RNAi on the therapy of leukemia.Methods:Small interfering RNA ( siRNA) for MMP-9 gene was designed and transfected into THP-1 cells.MMP-9 mRNA expression was assessed by RT-PCR, and MMP-9 protein expression was tested by Western blot.MTT and trypan blue staining were used to observe the effect on the proliferation of THP-1 cells after RNAi.The changes in cell morphology were observed under the microscope.Results:The expressions of MMP-9 mRNA and protein were inhibited in THP-1 MMP-9 siRNA-transfected cells ,significantly lower than those of control cells.The results of MTT and trypan blue staining in-dicated that the proliferation ability of THP-1 cells obviously decreased after siRNA-transfected 48h and 72h.The growth of cells was in-hibited and the cells survival rate was significantly lower than that of control group ( P<0.05 ).The cells of control groups grew semi-quote wall under inverted microscope.The outline of cells was clear and the shape was uniform.The cells grew vigorously.While the growth of cells in siRNA group was inhibited.The morphology of siRNA group cells changed obviously by the Wright staining.Most cells expressed changes of apoptosis.Conclusion: siRNA for MMP-9 gene can not only reduce the expressions of MMP-9 mRNA and protein,but also inhibit the proliferation and induce apoptosis of THP-1 cells.

Objective To evaluate the correlation between cerebral blood volume and permeability surface by using muhislice CT perfusion imaging with glioma grade.Methods Ninteen patients with gliomas underwent conventional MR and multislice CT perfusion imaging preoperatively.These patients were divided into low grade and high grade groups which were correspond to WHO Ⅱ grade gliomas and WHO Ⅲ or Ⅳ grade gliomas respectively.CT data were transferred to on-line working station and processed to obtain time-signal curves,color perfusion maps and calculated perfusion parameters,including cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT)and permeability surfaces (PS)in tumoral parenchyma.Kruskal-Wallis test and correlation of CBV and PS was assessed by using SPSS 11.0 software.Results The median of CBV and PS in low-grade and high-grade glioma were 2.7, 6.5 ml/100 g;0.389,12.810 ml?100 g~(-1)?min~(-1),respectively,corresponding t value were 12.907, 13.500 with P

Objective To discuss Bushen Huoxue Prescription mechanism of action on follicular granulosa cell apoptosis of premature ovarian failure (POF) mice. Methods The mouse zona pellucida 3 as the antigen, multi-point injection of subcutaneous immunization BALB/c to female mice was used to establish autoimmune POF model. Forty clean female mice were randomly divided into blank group, model group, Estradiol Valerate group and Bushen Huoxue Prescription group. All medicine groups were given relevant medicine for gavage, while model and blank groups were given normal saline with the same amount for gavage for 15 days. After the treatment, ovary, uterus, and thymus were weighed, and the viscera index was calculated. An ovarian slice was taken and HE staining was used to observe granulosa cell apoptosis. The levels of E2, LH, and FSH were detected by using the radioimmunoassay method. RT-PCR was used to analyze Fas and Fas-L mRNA expressions in ovarian granulosa cells. Results Compared with blank group, the weight of ovary, thymus, and uterus decreased significantly (P<0.05, P<0.01);Serum E2 level dropped (P<0.01);levels of FSH and LH, and expressions of Fas and Fas-L mRNA increased significantly (P<0.01). Compared with model group, granulosa cell apoptosis significantly decreased, and ovary index, uterus index, and thymus index increased (P<0.05);serum E2 level increased (P<0.01);levels of FSH and LH, and expressions of Fas and Fas-L mRNA significantly decreased (P<0.05). Conclusion Bushen Huoxue Prescription can decrease expressions of Fas and Fas-L mRNA to inhibit cell apoptosis by adjusting the hormone level of hypothalamus-pituitary-ovarianaxis.

OBJECTIVETo analyze the expressed mRNA of the factor subunit A (FA) in monocyte in a hereditary factor (F) deficiency family.

METHODSThe F A mRNA of the proband and the other family members was analyzed by RT-PCR, semi-quantitative RT-PCR, cloning and sequencing. The three dimensional structure of the protein was predicted by SWISS-MODEL and viewed by RASMIOL.

RESULTS(1) A large in frame deletion from codons 11 to 279, spanning from exon 2 to 7 of F A (DelCD11-279), was identified in the proband at mRNA level and a truncated protein is predicted composed of 464 amino acids. Compared with the normal and the other families, the proband showed lower level of F A mRNA in RT-PCR. (2) SWISS-MODEL analysis showed that the truncated protein lacked the β-sandwich and a part of catalytic core, resulting in loss of the normal catalytic domains.

CONCLUSIONDelCD11-279 of F A mRNA is associated with hereditary F deficiency. The reduced expressing level of F A gene is one of the causes resulting in F deficiency in the patients.

Adolescent ; DNA Mutational Analysis ; Exons ; Factor XIII ; genetics ; Factor XIII Deficiency ; genetics ; Female ; Humans ; Male ; Pedigree ; RNA, Messenger ; genetics ; Sequence Deletion

Objective To investigate the relationship between insulin resistance and erythrocyte in- sulin receptors in patients with gout associated with macroalbruminuria(MAU).Methods FBG,PBG,FINS, P2hINS,CH,TG,HDL,LDL-c,UA and erythrocyte insulin receptors were determined in 44 patients with MAU,62 patients with normal MAU(NMAU).Results In MAU,the levels of FINS,TG,LDL-c and HOMA-IR were(16?4)mU/L,(2.5?0.6)retool/L,(3.2?0.5)mmol/L and 3.6~1.2 respectively.While they were(13?3) mU/L,(2.3?0.8)mmol/L,(3.0?0.5)mmol/L and 3.0~0.4 in NMAU group.The levels of FINS,TG,LDL-c and HOMA-IR were significantly higher in the MAU patients than those in NMAU patients(P

BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.

METHODSHHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.

RESULTSThe average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.

CONCLUSIONSThalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.

Animals ; Animals, Genetically Modified ; Female ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic ; drug therapy ; metabolism ; Thalidomide ; therapeutic use ; Transforming Growth Factor beta3 ; genetics ; Vascular Endothelial Growth Factor A ; metabolism ; Zebrafish

OBJECTIVETo evaluate the estrogenic activity of several kinds of Chinese herbal medicines.

METHODUse zoopery and reporter gene technique to study the estrogenic activity of five Chinese herbal medicines. Zoopery: weanling female Kunming mice weight 9-12 g were administrated botanical extracts of Selaginella tamariscina, Pinus Massoniana, Corallodiscus flabellate, Dryopteris sublaeta and Leonurus heterophyllus, the positive control group with Nilestriol tablets and control group with water, respectiely. On the eighth day, the animals were sacrificed and the uteri were separated solely and weighed. Reporter gene technique: Induce the expression of reporter gene controlled by ERE and measure the activity of luciferase on cell's clear supernatant.

RESULTThe botanical extracts of S. tamariscina can increase weights of mice (P < 0.01); In the expression of reporter gene controlled by ERE, Either ERalpha or ERbeta's has estrogenic activity (P < 0.01). Follow in the zoopery we find the water part and the n-butanol part of S. tamariscina are the two active parts.

CONCLUSIONS. tamariscina and it's water part and n-butanol part have estrogenic activities, effect on ERbeta is greater than ERalpha.

Animals ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Estrogen Receptor alpha ; metabolism ; Estrogen Receptor beta ; metabolism ; Female ; Leonurus ; chemistry ; Mice ; Organ Size ; drug effects ; Phytoestrogens ; isolation & purification ; pharmacology ; Pinus ; chemistry ; Plants, Medicinal ; chemistry ; Selaginellaceae ; chemistry ; Uterus ; anatomy & histology

OBJECTIVEGastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To sensitize gastric cancer cells to TRAIL, we treated gastric cancer MGC803 cells with TRAIL and cisplatin.

METHODSCell proliferation was measured using MTT assay. Cell apoptosis was determined by flow cytometry. Expression of proteins was analyzed by Western blot. The distribution of lipid rafts and death receptors was analyzed by immunofluorescence microscopy. MGC803 cells were pretreated with 50 mg/L nystatin for 1 h, and followed by the treatment of cisplatin and TRAIL.

RESULTS100 µg/L TRAIL resulted in (8.51 ± 3.45)% inhibition of cell proliferation and caused (3.26 ± 0.89)% cell apoptosis in MGC803 cells. Compared with the treatment with cisplatin alone, treatment with TRAIL (100 µg/L) and cisplatin (8.49 mg/L, IC(50) dose of 24 h) led to a dramatic increase in both inhibition of cell proliferation [(52.58 ± 4.57)% vs. (76.43 ± 5.35)%, P < 0.05] and cell apoptosis [(23.10 ± 3.41)% vs. (42.56 ± 4.11)%, P < 0.05]. Moreover, cleavage of caspase-8 and caspase-3 was detected. TRAIL (100 µg/L) did not induce obvious lipid rafts aggregation and death receptor 4 (DR4) clustering, while cisplatin (8.49 mg/L) significantly promoted the localization of DR4 in aggregated lipid rafts. Pretreatment with 50 mg/L nystatin, a cholesterol-sequestering agent, triggered (3.66 ± 0.52)% cell apoptosis after 24 h. Pretreatment with nystatin for 1 h before the addition of 8.49 mg/L cisplatin for 24 h caused a decreased tendency to cell apoptosis [(25.74 ± 3.28)% vs. (22.76 ± 2.97)%]. While, pretreatment with nystatin before the addition of cisplatin and TRAIL, the proportion of apoptotic cells decreased from (43.16 ± 4.26)% to (31.52 ± 3.99)% (P < 0.05).

CONCLUSIONCisplatin enhances TRAIL-induced apoptosis in gastric cancer MGC803 cells through clustering death receptors into lipid rafts.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Membrane Microdomains ; metabolism ; Nystatin ; pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology