Background and purpose:Aurora-A is a member of serine/threonine kinase family. The abnormal expression of Aurora-A induces tumorigenesis and radioresistance. This study was aimed to investigate the association of Aurora-A with radioresistance. Methods: Capan-1 cells were treated with Aurora-A kinase inhibitor, and then used to test cell proliferation, anchorage independent assay, cell cycle, and cell cycle regulatory proteins. Treated cells were also used to detect cell apoptosis afterγ-irradiation. Results:Cell growth and colony number in soft agar were decreased after treatment with Aurora-A inhibitor. Treatment of cells with Aurora-A inhibitor also down-regulated the expression of Cyclin D1, CDK2 and CDK6 to induce cell cycle arrest at G1/S and G2/M phases, but promoted cell apoptosis afterγ-irradiation. Conclusion:Treatment of pancreatic cancer cells with Aurora-A kinase inhibitor blocks cell proliferation and cell cycle progression, and promotes sensitivity of cells to radiation. Thus, Aurora-A may be used as one of therapeutic targets to increase the sensitivity of pancreatic cancer radiotherapy.

Objective To investigate the effect of Erhuang decoction on TGF-β1 expression of lung tiusses and the concentrations of IL-33 in asthmatic rats. Methods Fifty Sprague-Dawley rats were randomly divided into five groups equally:Control group, Asthmatic group, Budesonide aerosol group, High-dose Erhuang decoction group ( 68 g/kg)and Low-dose Erhuang decoction group(17 g/kg). The model of asthma was established by ovalbumin (OVA) sensitizing and challeng-ing. Then Erhuang decoction and budesonide aerosol was used respectively for intervention therapy. Histologic HE staining were used to observe the general pathologic alteration and to analyze the total bronchial wall area (Wat) and the muscle wall area(Wam). The protein expressions of TGF-β1 in the lung tissues were detected by immunohistochemistry. The concentra-tions serum IL-33 and BALF were tested by sandwich ELISA. Results There was significant reduction in the infiltrated inflammatory cells in all drug intervention groups compared with asthma group;The Wat and Wam in asthmatic group was significantly higher in than those in Budesonide aerosol group,High-dose Erhuang decoction group and Low-dose Erhuang decoction group ( Watμm2/μm:54.99±8.82, 52.28±7.61, 58.53±7.63 vs 79.50±5.64, P＜0.05;Wamμm2/μm:22.74±2.73, 20.63±1.72, 21.20±4.50 vs 30.16±1.68, P＜0.05);Compared with control group, BALF and serum IL-33 concentration were significantly higher in asthmatic group. Compared with asthmatic group, all the indicators were significantly decrease in the treatment groups after drug intervention (P＜0.05). Andthere was no significant difference between the treatment groups in all the indicators. TGF-β1 expression in lung tissues in asthmatic group were significantly higher than that in control group (12.60 ± 2.25 vs 1.67 ± 0.17). Compared with asthmatic group, there was significantly reduction of TGF-β1 expression in the Budesonide aerosol group (5.51±2.48), High-dose Erhuang decoction group (5.22±2.52) and Low-dose Erhuang decoction group (6.92 ±2.18) (P＜0.05). There were no significant difference between the treatment groups. TGF-β1 expression and se-rum IL-33 concentration in asthmatic rats were positively correlated with Wat and Wam. Conclusion The effects of Er-huang decotion on ameliorating the progression of airway remodeling about asthmatic rats may be partially by regulating TGF-β1 and IL-33.

Objective To explore the effects of cotransplantation with osteoblasts on hematopoietic reconstitution in mice after bone marrow transplantation (BMT). Methods The typical model of syngeneic BMT was established. 18 Balb/c mice were used to prepare the bone marrow nuclear cells and osteoblasts for BMT. The 42 Balb/c mice were randomly divided into 3 group:normal group (6 mice, without any treatment), the single BMT group ( 18 mice, given 2 × 106 bone marrow nuclear cells/each mouse) and the cotransplantation group of HSC with osteoblaats (18 mice,given 2 × 106 bone marrow nuclear cells and osteoblasts/each mouse). The following factors were measured on day 7, 14, 21 after BMT: peripheral blood cells, bone marrow mononuclear cells (BMMNC), the percentage of CD34+ cells in BMMNC (assayed by flow cytometry), the hematopoietic tissue changes (detected by HPIAS-1000 image analysis system) and micro vascular density (MVD) of bone marrow tissue (with immunohistochemistry). Results The levels of periphral WBC, RBC, PLT, BMMNC in the contransplantation group were higher than those in the single BMT group (P＜0. 01 or P＜0. 05). In the contransplantation group, the percentage of CD34+ cells in BMMNC, the hematopoietic tissue area and the MVD of bone marrow were also higher than the single BMT group on the 7th, 14th, 21st day after BMT(P＜0.01 or P＜0.05). Conclusion Cotransplantation with osteoblasts could significantly promote hematopoietic reconstruction in mice after BMT. Cotransplantation may represent a promising means of achieving higher engraftment rate after BMT.

Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.

Objective To investigate the effects and the mechanism of telmisartan and pyridoxamine on oxidative stress in spontaneously hypertensive rats(SHR).Methods SHRs(male,20 weeks of age) were randomly divided into four groups (n＝ 12 for each):hypertension control (HC) group (2 ml of distilled water),telmisartan group[T,6 mg/(kg · d)],pyridoxamine group[P,200 mg/(kg · d)]and combined group(TP,6 mg/kg telmisartan and 200 mg/kg pyridoxamine per day).Treatments were continued for 16 weeks.The normal control group included 13 WKY rats and received gastric lavage with distilled water.SBP of tail artery was measured during the intervention ervey 2 weeks.The levels of AGEs,SOD and MDA were measured by ELISA,xanthine oxidase and thiobarbituric acid methods after the intervention.Expressiones of NF-κBp65,ERK1 and ERK2 in renal tissue were detected by immunohistochemistry.Expression of RAGE in the renal cortex was investigated by Western blot.Results SOD activity was decreased in the HC group.The levels of AGEs,MDA,RAGE and the activations of NF-κBp65 and ERK1/2 were increased in the HC group (t＝4.53,5.52,2.93,al1 P＜0.05).After the 16 weeks' intervention,SOD activity was elevated in T,P and TP groups compared to that in HC group (P＜0.05).The positive expressiones of NF-κBp65,ERK1 and ERK2 were significantly reduced in T,P and TP groups compared to those in HC group (F＝20.13、148.82、18.70,all P＜0.05).All the positive expressiones of NF-κBp65,ERK 1and ERK2 were lowest in the TP group versus T and P groups (t ＝ 3.58、2.84,P ＜ 0.05).Conclusions Telmisartan and pyridoxamine can alleviate the oxidative stress in spontaneously hypertensive rats,which may result from the blocking effect of Ang Ⅱ,the reduction of AGEs-RAGE and inhibiting the signal pathways of ROS,NF-κBp65 and ROS-ERK1/2.

To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
Bone Marrow Cells/metabolism ; Fibroblast Growth Factor 2/*biosynthesis ; Hematopoiesis/drug effects ; Pyrazines/*pharmacology ; Radiation Injuries, Experimental/*metabolism ; Radiation-Protective Agents/pharmacology ; Receptors, Fibroblast Growth Factor/*biosynthesis

To investigate p120 catenin mRNA expression in Non-Hodgkin's lymphoma (NHL) cell lines (U937, Raji, Jurkat and Molt4) and normal lymphocytes and explore the relationship between p120 catenin and Non-Hodgkins lymphoma, total RNA sample was extracted by using TRIzol and reversely transcripted into cDNA. Polymerase chain reaction was performed to detect mRNA expression of p120 catenin in NHL cell lines U937, Raji, Jurkat and Molt4. Normal lymphocytes were used as control. It was found expressions of p120 catenin 1A and 3A mRNA were high in above-mentioned NHL cell lines, but neither p120 catenin 1A nor 3A was found in normal lymphocytes as shown by RT-PCR. It is concluded that both P120ctn1A and P120ctn3A mRNA transcripts were found in all NHL cell lines U937, Raji, Jurkat and Molt4 but they don't exist in normal lymphocytes, suggesting p120ctn possibly is of importance in diagnosis and therapy of lymphoma.
Catenins/genetics ; Cell Adhesion Molecules/*genetics ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Jurkat Cells ; Lymphoma, Non-Hodgkin/genetics ; Lymphoma, Non-Hodgkin/pathology ; Phosphoproteins/*genetics ; RNA, Messenger/genetics ; RNA, Messenger/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Markers, Biological/genetics ; U937 Cells

Objective To study the effects of exogenous hormones,gibberellin(GA3)and indole-3-acetic acid(IAA),on growth and tanshinones accumulation in the radix of Salvia miltiorrhiza.MethodsThe herb characters and contents of tanshinones(cryptotanshinone,tanshinone Ⅰ,and tanshinone ⅡA)in the radix of S.miltiorrhiza with different hormone treatments were investigated and compared in the combination of trail pot and indoor analysis.Results It promoted aboveground biomass in the radix of S.miltiorrhiza increasing with single GA3.But it inhibited underground biomass increasing.The exogenous addition of low-level and high-level GA3 was benefit for tanshinones accumulation,whereas the middle-level GA3 wasn't.The aboveground and underground biomass in the radix of S.miltiorrhiza increased indistinctively with the increasing of IAA concentration and then decreased.And the IAA solutions also increased plant height and root length indistinctively.in a whole,it was benefit for tanshinones accumulation when applying low-level IAA(0.5 mg/L)singly.With the increasing of IAA concentration,the content of cryptotanshinone increased,but the contents of tanshinone Ⅰ and tanshinone ⅡA decreased.It promoted S.miltiorrhiza radix growth and three tanshinones contents increasing obviously with the combined application of two low-level hormones.Conclusion The applying of GA3 and IAA is benefit for the growth and three tanshinones accumulation in the radix of S.miltiorrhiza.

To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro-vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU-S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine-treated group, the diameter of center veins and the area of micro-vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT (P < 0.01). In addition, Ligustrazine significantly increased the number of CFU-S on day 10 and the number of CFU-GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.
*Bone Marrow Transplantation ; Hematopoiesis/*drug effects ; Hematopoietic Stem Cells/*drug effects ; Mice, Inbred BALB C ; Pyrazines/*pharmacology ; Time Factors

The kinetic changes in morphology and cellular density of epidermal Langerhanscells (LC) in the guinea pig were observed by ATPase cytochemical staining techniqueafter repeated skin application of 5%,3% and 1% of benzalkonium bromide (BB,primary irritant) and 0.05% dinitrochlorobenzene (DNCB,allergen) respectively.We have found that there was a significant difference in the density and morpho-logical change of LC between BB and DNCB application.Treatment with 5% BBcould induce a reversible decline in LC density and changes in cell processes,andwith 0.05% DNCB,the number of LC was decreased and the ATPase activity wasweakened only in the late stage of treatment.The significance of using the kineticchanges in morphology and cellular density of LC as the criteria for the safetyevaluation of weak allergens and weak primary irritants as well as cosmetics wasdiscussed.