OBJECTIVETo observe and analyze the antitumor effect of endostar combined with docetaxel under different administration sequences.

METHODSNude mice with xenograft tumor (A549 cell line) were randomized into 3 groups, 8 mice/group: (1) Concurrent administration group (each mouse: endostar 400 µg/d, d1-d35, docetaxel 10 mg/kg, every 3 days, d1-d19); (2) Endo-first group (each mouse: endostar 400 µg/d, d1-d35, docetaxel 10 mg/kg, every 3 days, d16-d34); (3) Model group (positive control, tumor-bearing mice without treatment, each mouse: physiological saline, 100 µl/d, d1-d35, water for injection, 200 µl/d, d1-d35, every 3 days), and blank control group (negative control, normal mice without treatment, 8 mice), the administration method was the same to the model group. The volume of tumor and the weight of mouse were measured during treatment. Circulating endothelial cells (CECs) were detected by flowcytometry, and the expression of matrix metalloproteinase (MMP-2, MMP-9), the tissue inhibitor of MMP (TIMP-1, TIMP-2), the extracellular MMP inducer (EMMPRIN), CD34, α-smooth muscle actin (α-SMA) were determined by immunohistochemistry.

RESULTSThe tumor growth of concurrent administration group (39.94 mm(3)) was lower than that of the endo-first group [(99.57 ± 74.48) mm(3)] during treatment, both of them were smaller than that of the model group [(217.67 ± 95.44) mm(3), P < 0.05]. The amount of CECs in the endo-first group [(77.25 ± 24.02) cells/10(4) cells] was more than that of the concurrent administration group [(25.86 ± 11.77) cells/10(4) cells], the model group [(14.71 ± 11.07) cells/10(4) cells], and the blank control group [(12.90 ± 11.20) cells/10(4) cells, P < 0.01]. The expression of MMPs in the treatment groups was obviously downregulated. The expressions of TIMP-1 in the endo-first group and TIMP-2 in the concurrent administration group were upregulated (P < 0.05). The expression of EMMPRIN was significantly down-regulated in the concurrent administration group (P < 0.05). The MVD and α-SMA expressions of the treatment groups were less than that of the model group (P < 0.05).

CONCLUSIONIn comparison with the endo-first group, the anti-tumor effect and survival quality of the concurrent administration group are better. Both of the administration groups may have "vascular normalization effect" by down-regulating MMPs expression through different points, and inhibit the cancer-induced stromal reaction, restraining the cancer progress to a certain extent. The changes of CECs should be a dynamic process with an initial rise in the early-stage suggesting the decrease of vascular bed and subsequent decline ascribed to apoptosis of CECs and the tumor-regression after combined therapy. Investigation of its dynamic changes may be helpful to know the change of tumor burden and vascular bed and predict the antitumor effect.

Actins ; metabolism ; Angiogenesis Inhibitors ; administration & dosage ; pharmacology ; Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Basigin ; metabolism ; Cell Line, Tumor ; Drug Administration Schedule ; Endostatins ; administration & dosage ; pharmacology ; Endothelial Cells ; cytology ; Female ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; drug effects ; Neoplasm Transplantation ; Taxoids ; administration & dosage ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects

Objective:To investigate the protective effects of Lactobacillus casei Zhang ( Lcz) on mice with Acetaminophen (APAP)-induced acute liver injury.Methods:Mice were randomly divided into five groups:Control group (ctrl),APAP-induced liver injury group ( APAP ) , N-Acetylcysteine positive control group ( NAC ) , Lcz preventive group ( Lcz/APAP ) and Lcz control group (Lcz).Mice were orally administrated with Lcz (1×109 CFU/ml) for 30 continuous days prior to APAP exposure.Positive control group were intraperitoneally injected with 150 mg/kg NAC 1 h before APAP challenge.Mice in the APAP,NAC and Lcz/APAP group were intraperitoneally injected with 300 mg/kg APAP.Blood and liver samples were collected 18 h post APAP challenge.The expression of HO-1,SOD2,Bcl-2 and TLR4 were detected by Western blot.Results: Lcz could significantly inhibit APAP-induced increase in ALT and AST levels.Furthermore,pretreatment with Lcz increased the hepatic expression of HO-1,SOD2 and Bcl-2,while suppressing the expression of Toll-like receptor 4 (TLR4).Conclusion:Lcz can protect against APAP-induced acute liver injury in mice.The hepato-protective effects of Lcz are associated with its anti-oxidative and anti-inflammatory capacity.

OBJECTIVETo detect and study the types of Borrelia burgdorferi sensu lato in ticks and rodents from Da Xing-An Mountains Forest areas of China.

METHODSNested PCR was performed to amplify 5S-23S rRNA intergenic spacer of B. burgdorferi. Positive products were analysed by restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP), specimens showing unique RFLP profile were sequenced and analysed.

RESULTS1336 Ixodes persulcatus, 144 Dermacento silvarum, 144 Haemaphysalis concinna and 145 rodents of 9 species were collected from 16 sections of Da Xing-An Mountains Forest areas of China. Specific fragments were amplified from 293 I. persulcatus and 6 D. silvarum and 5 rodents of 4 species. B. burgdorferi was not detected in H. concinna. Among the positively tested I. persulcatus, 209 contained B. garinii genospecies and 45 contained B.afzelii genospecies based on RFLP. Moreover, B.garinii genospecies consisted of B. garinii 20047 and B. garinii NT29. 17 adult I. persulcatus were simultaneously infected with B. garinii 20047 and B. garinii NT29. Nine adult I. persulcatus were simultaneously infected with B. garinii 20047 and B. afzelii. Four adult I. persulcatus were simultaneously infected with B. garinii 20047 and B. garinii NT29 and B. afzelii. Two D. silvarum were infected with B. garinii 20047, 1 D. silvarum with B. garinii 20047, 2 D. silvarum with B. afzelii. 3 rodents were infected with B. garinii 20047 while 2 rodents were infected with B. garinii NT29. Mixed infection was not found in D. silvarum and rodents. In addition, nine I. persulcatus and one D. silvarum specimens showed unique RFLP pattern. Data from sequential analysis showed that they all belonged to B. garinii. PCR-SSCP profiles of 5S-23S rRNA intergenic spacer of B. burgdorferi in the positive specimens exceeded 36 types; B. garinii 20047 showed 16 types while B. garinii NT29 showing 11 types, B. afzelii showing 9 types. SSCP profiles of the specimens coinfected with multiple B. burgdorferi was relatively complex.

CONCLUSIONThe infection of B. burgdorferi was found in the ticks and rodents in Da Xing-An Mountains Forests areas. The infection rate of I. persulcatus was high. B. garinii was predominant genospecies, and the population of B. burgdorferi was heterogeneous in the area. Mixed infections of different B. burgdorferi genospecies in ticks were found. I. persulcatus and Clethrionomys rufocanus were possibly served as major vector and major host for B. burgdorferi, respectively, suggesting that further study is needed to confirm the coinfection in humans and animals in this region.

Animals ; Borrelia burgdorferi Group ; genetics ; isolation & purification ; China ; epidemiology ; Humans ; Lyme Disease ; epidemiology ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single-Stranded Conformational ; RNA, Bacterial ; analysis ; Rodentia ; microbiology ; Ticks ; microbiology ; Trees

Objective To investigate the modulatory effect of substance P (SP) on proton-gated current in the membrane of rat trgeminal ganglion (TG) neurons and its underlying mechanism. Methods Neurons were isolated mechanically and enzymatically from TG of rat. Whole-cell patch clamp technique was used for recording the proton-gated current in freshly isolated neurons. Results Proton-gated currents recorded from rat TG neurons could be classified into 4 distinct types: T-type, S-type, B-type and O-type in the present study. Co-application of SP and proton potentiated S-type proton-gated currents in a concentration-dependent manner, and the potentiation was not blocked by SP receptor antagonist, GR82334; co-application of SP and proton potentiated B-type proton-gated currents, and GR82334 and intracellular dialysis of GDP-β-S blocked the potentiation of SP. Pre-application of SP inhibited B-type proton-gated current, especially the transient component. The inhibition could not be reversed by pretreatment wit-h GR82334. Conclusions The mechanisms of modulation of proton-gated current by SP is associated with the difference of their makeup of subunits of acid-sensing ion channels (ASICs), and there may be an allosteric position of SP in the outside framework of ASICs in neuronal membrane.

OBJECTIVETo investigate the prevalence of Anaplasma phagocytophilum in rodents from forest areas in northeastern China.

METHODSPCR amplification, followed by sequence analysis was carried out. The sequences of 16S rRNA and gltA gene fragment amplified from rodent specimens were compared with corresponding part of the sequences deposited in GenBank.

RESULTSA total number of 276 rodents were tested, including 102 in Jilin province, 61 in Helongjiang province and 113 in Inner Mongolia autonomous region. The positive rates were 8.82%, 1.64% and 0.00%, respectively. The infection rate in rodents infected by ticks was 11.30 times higher than that in rodents without ticks (P = 0.002). The S. A. phagocytophilum 16S rRNA sequences from rodents in Jilin and Heilongjiang were identical and differed in 3-5 bases compared with the corresponding parts of A. phagocytophilum from America, Sweden and Japan. Compared with the sequences registered in GenBank, the nucleotide sequence of gltA varied from 87%-97% and its deduced amino acid sequence changed from 84%-99%.

CONCLUSIONA. phagocytophilum infection was presented in rodents from Jilin and Heilongjiang province.

Amino Acid Sequence ; Anaplasma phagocytophilum ; genetics ; isolation & purification ; Animals ; Bacterial Proteins ; analysis ; Base Sequence ; China ; Ehrlichiosis ; veterinary ; RNA, Ribosomal, 16S ; analysis ; Rodentia ; microbiology ; Ticks ; Trees