Mastoparan(MAS) and α-latrotoxin(α-LTX) are two kinds of insulinotropic peptides obtained from insect toxins which can interact with islet β-cells and induce insulin secretion. The signal mechanism of these insulinotropic peptides regulating insulin-releasing attracts notable attention and has been elucidated more and more details. MAS mainly acts on the molecular components of exocytosis at a late stage. Insulin secretion induced by MAS is obviously dependent on GTP, which subsequently activates G-protein located on insulin secretion granules(ISG), or activates the Rho subfamily of small G proteins to evoke exocytosis and sensitize fusion machinery. The MAS stimulated insulin-releasing activity can be augmented by nutrients. However, its effect is not Ca~(2+) dependent. There are two regulatory pathway triggered by α-LTX: one way is pore formation caused through plasma membrane, another way is the transmembrane signal transduction evoked by cytosolic second messengers. Tetrameri complexs assembled at high concentration of α-LTX toxin or in the presence of extracellular Ca~(2+), can insert α-LTX into plasma membrane to form Ca~(2+) permeable channels and trigger Ca~(2+)-dependent secretion. By binding to transmembrane receptors and activating phospholipase C, α-LTX induces the generation of second messenger DAG and IP3. IP3 triggers Ca~(2+) influx and subsequently activates CaMK pathway, however, DAG also activates PKC pathway to increase insulin release.

Protein biochips industry has been making significant progress recently. It played a role in the discovery-oriented proteomics, but now the research emphasis turns to the study of important functional proteins. The emergence of the low density protein biochip technique facilitated this study conversion. This technology has advantages of low cross-reaction, high signal intensity and good precision. This paper reviewed various medical and pharmaceutical applications of the low density protein biochips in disease diagnostics and monitoring, drug discovery and testing, as well as molecular interaction and signaling pathways.

A? plays a crucial role in Alzheimer's Disease and the soluble A? oligomers have been recognized as the emerging neurotoxins,which ultimately cause memory impairment and neuronal loss through different mechanisms.The development of novel drugs targeting A? oligomers indicates new and promising therapy approaches for AD.The pathological roles as the proximal toxins in AD and the compounds,targeting soluble A? oligomers,which are currently in preclinical and early clinical development,are reviewed.

Objective In order to explore the localization of NGB mRNA in adult rat brain. Methods In the present study,the localization of NGB mRNA in brain of the adult rat was examined by in situ hybridization histochemistry using digoxigenin labelled cRNA probes. Results Transcripts of NGB mRNA were showed to be widely distributed throughout the adult rat brain,including cerebral cortex,hippocampus,thalamus,hypothalamus,cerebellum and olfactory bulb.Conclusion\ Our result suggested that NGB gene might play an important role in the central nervous system,possibly related to the oxygen supply of the neuron.

Objective To investigate fluorescence intensity of lipid ultrasound microbubbles constructed in vitro and targeted to leukaemia inhibitory factor receptor (LIFR) with a monoclonal antibody.MethodsThe LIFR-targeted ultrasound mierobubbles (MB-BSB-LIFR-AB) were constructed using a technology of biotin-avidin bridge.FITC labeled Avidin was incubated with lipid ultrasound microbubbles (MB) and biotinylated lipid microbubbles (MB-B).Two dilutions (1:4 and 1:16) of DTAF second antibody were incubated with four types of ultrasound microbubbles,including MB,MB-B,biotinavidin-MB (MB-BS),MB-BSB-LIFR-AB.The fluorescence intensity of microhubbles were graded as 0,1,2to 3.ResultsAfter incubating with FITC-avidin,MB-B displayed bright green fluorescence ( grade 3),but MB had no fluorescence ( grade 0).After incubating with two dilutions of DTAF second antibody (1:4 and 1:16),MB-BSB-LIFR-AB displayed brightest green fluorescence (grade 3) in both concentration,while MB-BS and MB-B only displayed dim green fluorescence (grade 1 ) at the dilution of 1:4,with MB displaying no fluorescence at either dilution (grade 0).Conclusions LIFR monoclonal antibody can be effectively conjugated to MB-B with biotin-avidin bridge.Fluorescence detection is a simple method for investigating the conjugation reliability of targeted lipid ultrasound microbubbles.

BACKGROUND: Previous research has investigated the effect of nano-zirconium dioxide-toughened hydroxyapatite (nano-ZrO2-HA) on the proliferation and differentiation of rabbit bone marrow stromal cells.OBJECTIVE: To evaluate the biocompatibility of nano-ZrO_2-HA compound.METHODS: The experiments of acute toxicity,subacute toxicity,pyrogen,hemolysis,and intramuscular implantation were performed on New Zealand rabbits,healthy adult Kunming mice,and adult rats according to "Technical Evaluation Standards of Biomedical Materials and Medical Instruments",promulgated by Chinese Board of Health.RESULTS AND CONCLUSION: Acute toxicity: All experimental animals survived.There was no significant difference in body mass before and after testing (P> 0.05).Pyrogen: Heating reaction was not tested.Hemolysis: Generally speaking,hemolytic crisis was not observed after 1 hour,and hemolytic rate was less than 5%.Intramuscular implantation: Infection did not occur in any animals,and materials were not discharged at all.Four weeks later,muscles were closely integrated with materials.A certain quantity of tissue grew into material pore,and peripheral muscle still had normal morphology and structure.Subacute toxicity:There was no significant difference in body mass and blood routine before and 2 weeks after testing.HE staining demonstrated that necrotic focus and other lesion were not observed in heart,liver,and kidney tissues under optic microscope.The results suggested that nano-ZrO_2-HA was non-toxicity,and it had no pyrogen and hemolysis effect,as well as it did not stimulate to the muscle of rabbit.Inflammatory rejection did not happen to the animal.The nano-ZrO_2-HA was closely integrated with the muscle,characterizing by great biocompatibility.Therefore,it can be used as substitution materials in clinical experiment.But it still needs to be evaluated completely.

Aim To investigate the antitumor and antiangiogenic effects of combined low-dose cyclophosphamide(CTX)and recombined VEGF protein vaccine.Methods In this experiment,H22 hepatocellular carcinoma model was established in BALB/c mice.Mice were randomly divided into four groups: control group,CTX group(CTX),VEGF protein vaccine group(V2)and CTX plus V2 group(CTX+V2).The anti-tumor efficacy and antiangiogenic effect were investigated using a subcutaneous tumor model and an intradermal tumor model.Western blot and ELISAwere further adopted to detect the specific anti-VEGF antibody.Results CTX+V2 group displayed a lower tumor volume and tumor weight than either the single therapy group in the subcutaneous tumor model(P<005 vs V2,P<001 vs CTX).Meanwhile,CTX+V2 was more effective for antagonizing tumor-associated angiogenesis compared with either the single therapy(P<005 vs V2,P<001 vs CTX).After CTX+V2 immunization,high titer of anti-VEGF antibody was detected by ELISA and verified by Western blot.Conclusion The therapy of CTX combined with V2 has significant synergistic effect against H22 hepatocellular carcinoma.

AIM: To investigate the effect of tea polyphenols (TP) on alcohol-induced liver injury in mice.METHODS: 40% alcohol(0 5 mL) and TP (5 mg) were administered intragastrically, the liver MDA level and serum alanine transaminase (ALT) activity were determined. The effect of TP on MDA level in alcohol-treated liver in vitro was also examined.RESULTS: Pretreatment with TP significantly inhibited alcohol-induced liver MDA increase in mice in vivo and in vitro , the increase in serum ALT induced by alcohol was also reduced by pretreatment with TP (0 5 mg). TP at a dose of 5 mg, administered 1 h after alcohol treatment, also suppressed increase in liver MDA level stimulated by alcohol. CONCLUSION: These results demonstrated that TP has a protective effect on alcohol-induced liver injury in mice.

Objective To investigate the effects of berberine on tumor-associated macrophages (TAM)and the expression of cyclooxygenase-2 (COX-2)of intestinal polyps in Apc(Min/+) mice.Methods A total of 20 Apc(Min/+) mice,four weeks old,were equally divided into the control group and the berberine group,10 in each group.The mice of the control group drank plain water,while the mice of berberine group drank water with 0.1 % berberine.After 12 weeks,all the mice were sacrificed.The intestine and colon were isolated,and the numbers of polyps were counted.The expression of F4/80,inducible nitric oxide synthase-2 (iNOS),macrophage mannose receptor (MR)and COX-2 was detected by immunohisto-chemistry method.The relative expression of COX-2 at protein level was measured by Western blotting. The t test was performed for comparison between two independent groups.Results The total number of intestinal polyps,the number of small intestinal polyps and the number of colon polyps of the berberine group (11 .50±2.05 ,10.50±1 .77 and 1 .00±0.46,respectively)were all less than those of the control group (30.63±1 .69,28.00±2.00 and 2.63±0.74,respectively),and the differences were statistically significant (t=16.727,16.952 and 3.162,P =0.001 ,0.001 and 0.010,respectively).The percentage of F4/80 positive cells in the stroma of polyps of the berberine group ((17.40 ±4.23 )%)was less than that of the control group ((31 .24±6.34)%),and the difference was statistically significant (t =5 .327, P =0.043).The percentage of iNOS positive cells in the stroma of polyps of the berberine group ((7.43± 1 .78 )%) was higher than that of the control group ((2.72±0.68)%), and the difference was statistically significant (t=7.335 ,P =0.004).The percentage of MR positive cells in stroma of polyps of the berberine group ((19.52±1 .54)%)was less than that of the control group ((12.63±0.68)%),and the difference was statistically significant (t=5 .634,P =0.016).The percentage of COX-2 positive cells in stroma of polyps of berberine group ((3.38 ± 0.51 )%)was less than that of the control group ((7.60±0.57 )%),and the difference was statistically significant (t = 7.234,P = 0.001 ).The relative expression of COX-2 at protein level of polyps of the berberine group was lower than that of the control group. Conclusion Berberine may take the role in inhibiting the growth of intestinal polyps in Apc(Min/+) mice through interfering the differentiation of TAM in polyps and suppression the expression of COX-2.