According to the results of activity-structure relationship (SAR) studies of alpha1-adrenoceptor antagonists hydantoin-phenylpiperazine and benzimidazo-arypiperazine derivatves, to design and synthesize a series of novel phenylpiperazine alpha1-adrenoceptor antagonists with more potent vasorelaxant activity, active metabolites of naftopidil were used as lead compounds. Ten novel R,S-1-substituted phenyl-4-[3-(naphthal-yl-oxy)-2-hydroxy propyl]-piperazine were designed and synthesized, their vasorelaxant activity was evaluated by calculating inhibition rate of phenylephrine-induced vasocontration of rabbit artery trips. Five compounds exhibited vasorelaxant activity, and compound 16 showed significant vasorelaxant activity in vitro. At 0.01 and 1 micromol x L(-1), its inhibition rates were 7.03% and 22.72%, respectively. This compound possessed ideal vasorelaxant activity in vitro, and would be selected for further anti-hypertension evaluation in vivo. Moreover, by analyzing the primary activity and structure relationship of these compounds, it could be concluded that the SAR results of the reported phenylpiperazine alpha1-adrenoceptor antagonists could be used for reference in designing novel derivatives of naftopidil with optimal pharmacological properties.
Adrenergic alpha-1 Receptor Antagonists ; Animals ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; In Vitro Techniques ; Molecular Structure ; Piperazines ; chemical synthesis ; chemistry ; pharmacology ; Rabbits ; Structure-Activity Relationship ; Vasoconstriction ; drug effects

Objective To explore whether puerarin induced apoptosis of SKOV3 ovarian cancer cells by microRNA-125b.Methods Using the qRT-PCR technique to detect the change of microRNA-125b after puerarin pretreated SKOV3.Using RNA interference technology to inhibit microRNA-125b expression in SKOV3 cells.Using Western blot technique to detect apoptosis related proteins after microRNA-125b lower expression.Results Puerarin could significantly inhibit ovarian cancer cell SKOV3 proliferation activity and promote its apoptosis related proteins expression.And puerarin can promote the expression of microRNA-125b.Inhibition of microRNA-125b expression in ovarian cancer cell SKOV3 could reduce apoptosis protein expression in SKOV3 cell.Conclusion MicroRNA-125b was involved in puerarin induced SKOV3 cell apoptosis,and prompt microRNA-125b is key molecular of the drug resistance in SKOV3.

OBJECTIVETo investigate the expression of heparanase mRNA and its relation with the clinicopathological features and angiogenesis in primary hepatocellular carcinoma (HCC).

METHODSExpression of heparanase mRNA was detected by RT-PCR in 51 HCC lesions, and microvessel density (MVD) was detected by immunohistochemical stain with a factor VIII-related monoclonal antibody.

RESULTSExpression of heparanase mRNA was shown in 49.0% (25/51) HCC lesions. The positive rate of heparanase expression in tumors larger than 3 cm (63.6%, 21/33) was significantly higher than those in smaller tumors (22.2%, 4/18; P < 0.01). Heparanase expression was more frequent in highly invasive tumors (70.0%, 14/20) compared with moderately invasive tumors (46.7%, 7/15) and low invasive ones (25.0%, 4/16; P < 0.05). Moreover, heparanase expression in tumors with high MVD (62.5%, 20/32) was significantly higher than those in tumors with low MVD (26.3%, 5/19; P < 0.05).

CONCLUSIONHeparanase mRNA expression may be important for the growth, invasion and angiogenesis of hepatocellular carcinoma.

Adult ; Carcinoma, Hepatocellular ; blood supply ; enzymology ; pathology ; Female ; Glucuronidase ; biosynthesis ; genetics ; Humans ; Liver ; enzymology ; Liver Neoplasms ; blood supply ; enzymology ; pathology ; Male ; Microcirculation ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; enzymology ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Burden

Four-stage selected random samples were used to analyze the prevalence and distributing feature of hyperuricemia and gout in 13 559 Han,Uighur,and Hazakh adults in Xinjiang. The prevalence of hyperuricemia was 11.00%,3.27%,and 3.94% respectively in Han,Uighur,and Hazakh populations,and 1.32%, 0.65%,and 0.70% for gout,with statistically significant difference among three groups(all P＜0.05). No-conditional logistic regression analysis showed that nationality,body mass index,renal function,and serum lipid were risk factors of hyperuricemia,while female and physical activity were protective factors. Eating seafood and animal visceral organs were independent risk factors of hyperuricemia in Han population. Eating animal visceral organs and drinking alcohol were independent risk factors of hyperuricemia in Hazakh population.

OBJECTIVETo explore the toxic effect of fluoride on the human thyroid cells (Nthy-ori 3-1) and its mechanism.

METHODSNthy-ori 3-1 cells were exposed to 0.0, 0.1, 1.0, 3.0 mmol/L of sodium fluoride (NaF) in vitro. After 24 hours incubation, 3 (4,5-Dimethylthiazol-z-yl)-3, 5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to measure cell viability and the LDH leakage rate. Reactive oxygen species (ROS) level, constituent ratio of the cell cycle, and apoptosis rate were measured by flow cytometry.

RESULTSComparing to viability of control group (set as 100.00%), the cell viability of the 1.0, 3.0 mmol/L fluoride-treated groups (76.64 +/- 9.13)%, (64.04 +/- 6.32)% were significantly decreased (all P values <0.01). LDH leakage rate and ROS level of the 3.0 mmol/L fluoride-treated group ((48.66 +/-7.15)%, (29993.50 +/- 1786. 86) FI) were significantly increased (all P values <0.01) compared to control group ((35.24 +/- 3.02)%, (13021.33 +/- 1067.55) FI). The G0/G1 phase cells of the 1.0 mmol/L fluoride-treated group ((40.76 +/- 5.65)%) were lower than control group (60.09 +/- 1.76)% (P < 0.01), yet the percentage of cells in S phase ((54.05 +/- 4.59)%) were higher than the control group (32.59 +/- 2.43) % (P < 0.01). Comparing to control group ((9.64 +/- 3.44)%), the percentage of apoptosis cells increased in the 3.0 mmol/L fluoride-treated group ((20.09 +/- 3.22)%) (P < 0.01).

CONCLUSIONTo Nthy-ori 3-1 cells, fluoride under experimental concentrations decreases cell viability, improve the LDH leakage rate, and ROS level. It blocks the cells in S phase and induce cell apoptosis.

Apoptosis ; drug effects ; Cell Cycle ; Cell Division ; Cell Line ; Fluorides ; toxicity ; Humans ; Reactive Oxygen Species ; analysis ; Thyroid Gland ; cytology ; drug effects

OBJECTIVETo study the optimum technology of extracting bioactive component named geniposidic acid in Eucommia Ulmiodes by orthogonal test.

METHODAn orthogonal test table L16(4(5)) was used with the factors of extracting time, temperature, times, ethanol consistency and the ratio of solid to liquid. The content of geniposideic acid was determined by RP-HPLC.

RESULTThe optimum technology was: temperature 50 degrees C, time 1 h, once, consistency 80%, and the ratio of solid and liquid 1:12. Under the condition, the best material of Eucommia Ulmiodes for extracting geniposidic acid was chosen.

CONCLUSIONThe technology can provide some theoretic advice for industry.

Chromatography, High Pressure Liquid ; Ethanol ; Eucommiaceae ; chemistry ; Glucosides ; analysis ; isolation & purification ; Iridoid Glucosides ; Iridoids ; analysis ; isolation & purification ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Technology, Pharmaceutical ; methods ; Temperature ; Time

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Biomarkers ; Female ; Interleukin-17 ; antagonists & inhibitors ; genetics ; Interleukin-6 ; genetics ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tripterygium ; Triterpenes ; pharmacokinetics ; pharmacology

OBJECTIVETo investigate the rules of proliferation of epithelial cells of sweat glands in deep partial-thickness burn wound and its transdifferentiation towards epidermal cells during healing process to explore its mechanisms.

METHODSTwenty-eight patients with limbs and trunk burn hospitalized in the Fourth People's Hospital of Taizhou City of Jiangsu Province and the Second Hospital of Shandong University from January 2004 to December 2007 were enrolled in the study. Tissue samples of deep partial-thickness burn wound (DPBW, n = 37), superficial partial-thickness burn wound (SPBW, n = 21), and normal skin (NS, n = 10) were harvested. Expressions of cytokeratin 10 (CK10), bcl-2, P63, CK14 and CK19 of epithelial cells in glandular secretory portion (GSP) in DPBW, SPBW and NS were detected with immunohistochemical double staining method.

RESULTSIn NS, CK19, CK14 and CK10 expressed in medium intensity in GSP epithelial cells, P63 and CK14 weakly expressed in basal myoepithelial cells, while no expression of bcl-2 or P63 was observed in all CK10 positive terminally differentiated cells. In SPBW, no change of the construction of GSP and above-mentioned proteins during healing process was observed. In DPBW, as examined on 7(th) post burn day (PBD), expression of P63 and bcl-2 in GSP epithelial cells was enhanced. In DPBW on 8 - 10 PBD, bcl-2, P63, CK19 and CK14 strongly positive solid island-like epithelial structure was formed by proliferation, migration and squamous epithelization of basal cells. Such structure, along with granulation tissue, migrated towards the superficial layer of wounds. The hyperplasia of squamous epithelium resulted in complete reepithelialization. In DPBW, bcl-2, CK14, CK19 and P63 still strongly expressed in hyper-proliferative epidermal basal and suprabasal layers on 13 - 30 day after healing.

CONCLUSIONSDuring the natural healing process of DPBW, monolayer epithelium (CK19 and CK10 positive) of GSP slowly develops into stratified squamous epithelium (bcl-2, P63, CK19, and CK14 positive), suggesting that the epithelial-epidermal transdifferentiation of GSP undergoes slow retrodifferentiation process of stem cells and transient amplifying cells, resulting in the imbalance between lagged growth of epithelium and the hyperplasia of granulation tissue, constituting one of the important mechanisms of disturbance in DPBW repair.

Adolescent ; Adult ; Burns ; metabolism ; pathology ; Cell Differentiation ; Epithelial Cells ; metabolism ; Female ; Humans ; Keratin-10 ; metabolism ; Keratin-14 ; metabolism ; Keratin-19 ; metabolism ; Male ; Membrane Proteins ; metabolism ; Stem Cells ; metabolism ; Sweat Glands ; cytology ; metabolism ; Wound Healing ; Young Adult ; bcl-2-Associated X Protein ; metabolism