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The application of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin(PA-MSHA)in the field of an-titumors has been increasing.PA-MSHA has been found to promote tumor cell apoptosis,inhibit tumor cell invasion and migration,differentiation,and change drug resistance and epithelial-mesenchymal transformation(EMT)by inhibiting the EGFR pathway.Meanwhile,PA-MSHA also enhances the immune killing and inhibition of macrophages and T cells to tumor cells through toll-like receptors(TLRs).In this paper,we reviewed the reported anti-tumor mechanism and clinical application of PA-MSHA,suggesting that PA-MSHA may alter the glycosylation of EGFR and TLR proteins by acting on the regulatory process of the cellular mannosy-lation process.PA-MSHA can act on cell membrane proteins,including more receptors with high-mannosylation of signaling path-ways.Elucidating the deep relationship between PA-MSHA and mannosylation is of great significance for the mechanism research and clinical application of PA-MSHA.
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The traditional model Franz diffusion cell method has always been the “gold standard” for evaluating the permeability of transdermal drug delivery system （TDDS） drug. However， in the high throughput screening of a large number of drug molecules， it has the disadvantages of low efficiency， high cost， difficulty to obtain isolated skin，poor reliability and large workload. The emergence of parallel artificial membrane permeation assay （PAMPA） model provides reliable pre-prediction data for the evaluation of permeability of TDDS drug. PAMPA model has been widely used in the permeability screening research of TDDS drugs and their preparations such as analgesics， local anesthetics， antioxidants， antipyretics， analgesics and anti-inflammatory drugs， vitamins， cholinesterase inhibitors， active ingredients of natural products， and has the characteristics of high reliability， good selectivity， high efficiency， low cost and data stability. PAMPA model has greatly improved the high throughput screening efficiency of TDDS drug permeability. With the extensive application and gradual maturity of this model， it will become a new and effective evaluation method in addition to the traditional evaluation model.
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Objective To investigate the effects of Ligustilide on the withdrawal syndromes syn-dromes and monoamine neurotransmitters of hypothalamus and nucleus accumbens in morphine-dependent rats. Methods Totally 60 SD rats were divided into control group,model group,clonidine group and Ligust-ilide high(80 mg/kg),medium(40 mg/kg) and low(20 mg/kg) dose group according to the random number table with 10 in each group. Rats were given in gradual increasing doses of morphine to produce physical de-pendence. Morphine withdrawal syndrome was precipitated by naloxone and withdrawal symptoms were evalu-ated by Ryuta Tomoji score. The level of norepinephrine ( NE), dopamine ( DA) and 5-hydroxytryptamine (5-HT) in rats were tested with enzyme-linked immunosorbent assay(ELISA). Results The total score of somatic withdrawal syndromes in the control group,model group,clonidine group and Ligustilide low,medium and high dose group were 0,(31. 83±7. 33),(17. 92±6. 88),(25. 58±5. 99),(19. 88±4. 82) and (16. 75 ±4. 01) . Compared with the model group,the morphine withdrawal syndromes scores of Ligustilide low,me- dium and high dose groups and clonidine group were reduced(all P<0. 05). The level of NE,DA and 5-HT in hypothalamus and nucleus accumbens were increased compared with that of control group. Compared with the model group,the level of NE,DA and 5-HT in hypothalamus and nucleus accumbens of Ligustilide low, medium and high dose groups and clonidine group were significantly reduced (P<0. 05). Conclusion Ligu-stilide can effectively alleviate the symptoms in morphine-withdrawal rats,which may be related to the inhibi-tion of excessive release of monoamine neurotransmitters in hypothalamus and nucleus accumbens.
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OBJECTIVE:To study induction effect of euphornin on the apoptosis of cervical cancer Hela cells and its mechanism. METHODS:The cervical cancer Hela cells were divided into blank control group,cisplatin group(positive control, 10 mg/L) and euphornin low-dose,medium-dose and high-dose groups (50,100,200 mg/L). They were treated with relevant medicine. The inhibitory effect of Hela cells proliferation was tested by MTT assay after 24,48,72 h of medicine treatment. The apoptotic rate of Hela cells was measured by flow cytometry after 48 h of medicine treatment. Morphology of nucleus was detected by Hoechst 33258 staining. The protein expression of Cyt-C,Bcl-2,Bax,Caspase-3,Caspase-8,Caspase-9 and Caspase-10 were detected by Western blot assay. RESULTS:Compared with blank control group,inhibitory rate of cell proliferation and cell apoptosis rate were increased significantly in cisplatin group and euphornin groups(P＜0.05 or P＜0.01),and obvious staining, deformation,shrinking,fragmentation or apoptotic bodies was found in nucleus. Compared with blank control group,the protein expression levels of Cyt-C,Caspase-8 and Caspase-9 in euphornin low-dose,medium-dose and high-dose groups were increased significantly,while the protein expression level of Bcl-2 and Bcl-2/Bax ratio were decreased significantly(P＜0.05 or P＜0.01);the protein expression levels of Bax,Caspase-3 and Caspase-10 in euphornin medium-dose and high-dose groups were increased significantly(P＜0.05 or P＜0.01). CONCLUSIONS:Euphornin can significantly inhibit the proliferation of Hela cell and promote cell apoptosis,the effect of which will be achieved by activating the Caspase-dependent mitochondrion apoptosis pathway.
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Objective To evaluate the effects of ganglioside GM1 on hypoxic ischemic brain damage (HIBD) in neonatal rats and on the expression of potassium-chloride cotransporter 2 (KCC2) in hippocampus.Methods Seven-day-old Sprague-Dawley (SD) rats (n=72) were randomly divided into a sham group,an HIBD group and a ganglioside GM1 group.Each group was further divided into a 3 d subgroup and a 21 d subgroup according to the different detection index (n=12).Rat HIBD models were prepared according the Rice-Vannucci method.After HIBD,the ganglioside GM1 group was given ganglioside GM1 20 mg/ (kg ·d) by intraperitoneal injection for 3 d continuously.2-,3-,5-triphenyltetrazolium chloride (TTC) was preformed to evaluate the area of cerebral infarction of HIBD in each 3 d subgroup.Spontaneous activity recorder was used to observe the locomotor activity of the rats in the 21 d subgroups.Morris water maze test was conducted for assessment of rats' learning and memory abilities in the 21 d subgroups.Western blot analysis was employed to determine the alterations in KCC2 expression in hippocampus in all the 3 d and 21 d subgroups.Results Compared with the HIBD group (28.6％±5.2％),the ratio of cerebral infarction volume in the ganglioside GM1 group (11.3％±2.4％) was significantly reduced (P＜0.05).Compared with the HIBD group (289.6±61.3),the number of locomotor activities within 2 h in the ganglioside GM1 group (412.1±66.8) was significantly increased (P＜0.05).Compared with the HIBD group,the escape latency was significantly reduced,but the percentage time of target quadrant and the number of crossing the platform were significantly increased in the ganglioside GM1 group (P＜0.05).Three days and 21 days after HIBD,the expression of KCC2 in the ganglioside GM1 group was significantly higher than that in the HIBD group (P＜0.05).Conclusion Ganglioside GM1 may have a significant protective effect on HIBD in neonatal rats,and its mechanism may be related to regulation of the expression of KCC2 in hippocampus.
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Objective To explore the effects of angelica naphtha on the withdrawal signs and norepinephrine neurotransmitter in uorphine-dependent rats.Methods 72 SD rats were randomly divided into control group,model group,clonidine group and three angelica naphtha groups (80,40 and 20 mg/kg).Rats were received gradualy increasing doses of morphine to produce physical dependence.Withdrawal symptoms were evaluated by Ryuta Tomoji score.The level of norepinephrine and normetanephrine(NMN) were tested by enzyme-linked immunosorbent assay(ELISA).Results The scores of withdrawal signs were (4.00± 3.29),(30.13±4.41),(18.96± 4.43),26.04±4.13),(22.33±4.60) and (19.00±3.47),respectively.The morphine withdrawal signs were reduced by angelica naphtha in a dose-dependent manner(P＜0.01),also significantly reduced the level of NE and NMN and the ratio of NMN/NE in the nucleus ceruleus and prefrontal cortex(all P＜0.01).Conclusion Angelica naphtha alleviates the withdrawal synlptons in morphine-dependent rats,which may be related to the inhibition of excessive turnover of norepinephrine neurotransmitters in the nucleus ceruleus and prefrontal cortex.
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Objective To investigate the effects of baicalin on morphine-induced behavioral sensitization.Methods Locomotor activity was measured for 2h after administration with baicalin in mice.Hyperlocomotion induced by acute morphine (10 mg· kg-1,ip) and behavioral sensitization induced by repeated morphine were established.The level of dopamine of ventral tegmental area(VTA) and prefrontal cortex(PFC) in mice was tested by ELISA assay.Results Baiealin inhibited significantly both locomotor activity in mice (control (1095.8 ± 174.5) times,baicalin (899.6± 187.2),(724.2± 221.4),(609.1 ± 154.6) times ; P＜ 0.01) and hyperlocomotion induced by acute morphine(model (1518.2± 185.8) times,baicalin (1385.4±224.2),(1205.1 ± 174.6),(1100.3±235.1) times ; P＜0.01).Similar inhibition was also seen in the development and expression of morphine-induced behavioral sensitization(model(2096.2±304.6) times,baicalin (2004.2 ± 218.5),(1998.7-± 224.3),(1836.1 ± 233.5) times,P＜ 0.05 ; model (2124.2 ± 189.6) times,baicalin (1922.2± 314.7),(1524.1±289.2),(1477.4± 219.3) times,P＜0.01).Baicalin inhibited dopamine release in VTA and PFC of morphine-sensitized mice(model(457.6± 92.1,589.2 ±102.5) μg · L-1,baicalin(391.1±56.8) μg · L-1,(448.6± 99.3) μg · L-1; (324.5±66.2) μg · L-1,(368.7±45.9) μg · L 1 ; (234.3± 52.6) μg · L-1,(305.3±84.1) μg · L-1 ; P＜0.01,P＜0.01).Conclusion Baicalin inhibits the development and the expression of morphine-induced behavioral sensitization in mice,and this effect is related to the inhibition of dopamine release in VTA and PFC of mice.