Advances in the role of neutrophil-derived reactive oxygen species in tumor / 医学研究生学报

Neutrophil is an important part of innate immune system, and plays a key role in resisting pathogen invasion and tumor immune surveillance. Meanwhile, neutrophil could produce reactive oxygen species , which are side products of cell metabolism. It is closely related to tumor development and progression. On the one hand, neutrophil could produce ROS to promote tumor growth and metastasis. On the other hand, it could also induce tumor cell death through different mechanisms. In this review, we summarize the roles of neutrophil- derived ROS in tumor development and discuss its prospects in cancer treatment.

Preparation and performance detection of small-diameter tissue-engineered blood vessels / 中国组织工程研究

BACKGROUND:Due to limited sources,poor hemocompatibility and poor anticoagulation performance,small-diameter tissue-engineered blood vessels cannot be applied in clinical practice.OBJECTIVE:To explore the physicochemical and mechanical properties of sheep carotid arteries after the decellularization in order to find appropriate materials for the preparation of tissue-engineered blood vessels.METHODS:Fresh carotid arteries from sheep were randomly divided into two groups:control group,in which,the sheep carotid arteries were cryopreserved for use after trimming and cleaning;experimental group,in which,after trimming and cleaning,the carotid arteries were decallularized by Triton X-100.sodium deoxycholate and EDTA for 24 hours,rinsed for 72 hours,digested with RNA/DNA enzymes for 24 hours,rinsed for 24 hours and reserved for later use.In both groups,blood samples were subjected to hematoxylin-eosin staining,collagen fiber staining,elastic fiber dyeing,and electron microscopy observation.The physical and chemical properties of the blood vessels are tested by tensile strength,wall tension and thickness.RESULTS AND CONCLUSION:(1) The collagen fibers in both two groups were neat and compact in alignment,with no obvious fracture.(2) Hematoxylin-eosin staining showed that:in the control group,the nuclei were distributed in the inner membrane,middle lamella and outer membrane of the vessels,and the fibers ran regularly;in the experimental group,the fibers ran in order but loosely,and there were no nuclei in the inner membrane,middle lamella and outer membrane of the vessels.(3) Elastic fibers in the control group were regular in alignment and mainly distributed in the middle lamella and outer membrane of the vessels,while in the experimental group,the elastic fibers ran regularly but loosely,and mainly distributed in the middle lamella and outer membrane of the vessels.(4) Under the scanning electron microscope,the originally formed vessels were observed in the experimental group,with no cell residues,and the collagen fibers ran orderly with no fracture and with uniform pore structure.(5) The vessel thickness was lower in the experimental group than the control group (P ＜ 0.01),but the tensile strength showed no difference between the two groups,which was 46.55 kPa in the two groups.To conclude,the decelluarized sheep carotid artery can retain the necessary mechanical properties of the blood vessels after achieving the maximum removal of antigenicity.

Role of autophagy in doxorubicin-induced cardiotoxicity:review / 中国药理学与毒理学杂志

Doxorubicin (Dox) is an effective wide-spectrum antitumor drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. The mechanisms of cardiotoxicity have not been clearly elucidated, but are known to involve oxidative stress, mitochondrial dysfunction and apoptosis. Autophagy is a lysosome-dependent protein degradation pathway. More recently, many studies have suggested that autophagy plays an important role in Dox-induced cardiotoxicity. This paper gives a systematic review of the role of autophagy in Dox-induced cardiotoxicity.

Simultaneous determination and pharmacokinetics of eight ginsenosides by LC-MS/MS after intravenously infusion of 'SHENMAI' injection in dogs

SHENMAI injection, a prescription comprised of Panax ginseng and Ophiopogon japonicas, is being extensively applied in the field of cardio-protection and immune-modulation in China. Ginsenosides are the main active components in SHENMAI injection. In order to capture and analyze the pharmacokinetic profile of major ginsenosides of SHENMAI injection in Beagle dogs, liquid chromatography equipped with electro-spray ionization and tandem mass spectrometry method was applied in simultaneous determination for protopanaxatriol type ginsenoside [Re, Rf, Rg1], protopanaxadiol type ginsenoside [Rb2, Rb1, Rd, Rc] and oleanolic acid type ginsenoside [Ro]. A C18 column [150 × 2.1mm, 5micro m] and a linear gradient program were used to achieve chromatographic separation, with 0.02% acetic acid solution and acetonitrile. I.S. and ginsenosides were detected by LC-MS/MS in selective reaction mode. Good linearity spanning 5- 1500ng/mL was achieved with the R[2] values higher than 0.99 for all analytes. Limit of quantification of all analytes were 3ng/mL. Intra- and inter-day precisions ranges from 0.47 to15.68 % and accuracies were within the range of 85.27-117.57%. Validated analyzing method was then used in the pharmacokinetic experiment for SMI in dogs. The results showed that the pharmacokinetic profile of protopanaxadiol, protopanaxatriol and oleanolic acid type ginsenoside were significant difference in dogs. Protopanaxadiol type ginsenosides exhibited an extremely higher level of exposure and a much slower elimination process. Whereas protopanaxatriol type ginsenosides were quickly eliminated. We concluded that 20 [S] - protopanaxadiol type ginseno sides could be a potential pharmacokinetic marker of SHENMAI injection

Inducing-apoptosis effect of brucine on human monocytic leukemia cell line THP-1 and its mechanism / 中国实验血液学杂志

This study was aimed to investigate the inducing-apoptosis effect of brucine on human monocytic leukemia cell line THP-1 cells and its possible mechanism. The inhibition effect of brucine on growth of THP-1 cells was measured by CCK-8 method. Morphological changes of THP-1 cells treated with brucine was detected by acridine orange/ethidium bromide (AO/EB)double staining. Annexin-V/PI double labeling method was used to assay the apoptosis rate of THP-1 cells. The effect of brucine on THP-1 cell cycle distribution was detected by PI single staining. RT-PCR was used to detect the expression of BCL-2 and BAX. The results showed that the brucine could inhibit the THP-1 cell growth in concentration and time-dependent manners at the range of 50 to 400 µg/ml. The cells stained with AO/EB revealed that the brucine induced the nuclear chromatin condensation. After the THP-1 cells were treated with brucine of 400µg/ml for 48 hours, most nucleic were stained as orange-red, and condensed, displaying the late apoptotic cell morphology. Annexin-V/PI detection showed that brucine could induce apoptosis of THP-1 cells in a concentration-dependent manner. Compared with the control group, more cells in brucine-treated group were arrested at G0/G1 phase in a concentration-dependent manner. RT-PCR detection revealed that the expression of BCL-2 was down-regulated strikingly and BAX was up-regulated. It is concluded that brucine can efficiently inhibit cell growth and block THP-1 cells in G0/G1 phase. The mechanism of THP-1 cell apoptosis induced by brucine may be related to the inhibition of BCL-2 and activation of BAX.

Research advances on caspase-independent cell death of K562 cells / 中国实验血液学杂志

Caspase independent cell death (CICD) is defined as death that ensues when a signal that normally induces apoptosis fails to activate caspases,it can be activated by PARP-1, Calpains, Bax and AIF, possessing distinctive biologic characteristic differed from apoptosis and necrosis. Recent researchs have found that the molecular mechanisms governing CICD of K562 is opposite from that of the traditional medicine killing leukemia cells, which may have the potential pharmaceutical point for new drugs. This article reviews the newly acquaintance of molecular mechanisms for CICD and recent studies concerning the induction death of K562 cells via CICD, so as to provide some reference for the research of new drug point.

Expression and significance of nitric oxide synthase in mandibular distraction osteogenesis of canine / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression and significance of nitric oxide synthase (NOS) during mandibular distraction osteogenesis and bone trauma healing, to futher study the mechanism of distraction osteogenesis.</p><p><b>METHODS</b>Twenty-eight adult dogs were randomly divided into DO group (12 dogs), acutely lengthening group (12 dogs) and control group (4 dogs). Immunohistochemical examination were carried out to test the expression of NOS during the sixth day in distraction period, the second and eighth week of consolidation.</p><p><b>RESULTS</b>In DO group infiltration of inflammatory cell was found in the distraction gap, more red blood cells (RBC) leak out around vascellum and matrix in the sixth day in distraction period. The expression of local iNOS (inducible NOS) and eNOS (endothelinal NOS) in DO gruoup and acutely lengthening group was higher than that in the control group (P < 0.05), the expression of local iNOS and eNOS in acutely lengthening group was lower than that in DO group (P < 0.05) in the early of distraction period and the consolidation. The expression of local iNOS and eNOS was no statistic difference between three groups (P > 0.05) in the eighth week of consolidation.</p><p><b>CONCLUSION</b>NOS as a sensitive index of tissue trauma are highly expressed, and RBC was found leaking out in the early of distraction, indicating that micro-trauma to some extent may occurr during DO procedure, the micro-trauma may be one of the significant factors which increasing regeneration of bone during DO.</p>

Cloning of human bone morphogenetic protein-2 gene and the construction of its eukaryotic expression vector / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To clone human bone morphogenetic protein-2 (hBMP2) gene and construct its eukaryotic expression vector pcDNA3.1 -hBMP2.</p><p><b>METHODS</b>Human BMP2 gene was amplified by RT-PCR method from human osteosarcoma cells and constructed into eukaryotic expression vector pcDNA3.1-hBMP2. The gene in the vector pcDNA3.1-hBMP2 was identified by PCR amplification, enzyme digestion and DNA sequencing.</p><p><b>RESULTS</b>The cloned DNA was confirmed to be hBMP-2 gene.</p><p><b>CONCLUSION</b>In this study, hBMP2 gene is successfully cloned and its eukaryotic expression vector pcDNA3.1-hBMP2 is constructed, which provides the foundation of using BMP2 gene therapy to accelerate new bone formation in distraction osteogenesis.</p>

Chiral pharmacokinetics and inversion of NG-nitro-arginine in rats / 中国药理学通报

Aim: To explore pharmacokinetics of NG-nitro-D-arginine (D-NNA)and NG-nitro-L-arginine (L-NNA)in conscious rats. Methods: The plasma concentration of D-NNA and L-NNA were determined by chiral ligand exchange method with capillary electrochromatography (CEC). Pharmacokinetic parameters were obtained using non-compartment model and were fitted using a computer program DAS. Results: The metabolism of D-NNA and L-NNA exhibited significant isomeric selectivity. The CL and T1/2 of D-NNA and D-NNA were(0.46 ± 0.02) ml·h-1·kg-1 vs (0.17 ± 0.03) ml·h-1·kg-1 (P < 0.05) and (1.44 ± 0.28) h vs (3.48 ± 0.41) h (P < 0.05), respectively. Unidirectional chiral conversion rate of D-NNA to L-NNA was (50.03 ± 8.5)%. Conclusion: The stereoselective pharmacokinetics of N G-nitro-arginine observed maybe due to the unidirectional chiral inversion of D-NNA to L-NNA.

The effect of dog bilateral distraction osteogensis in temporomandibular joint / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of bilateral mandibular distraction osteogenesis in the condyles.</p><p><b>METHODS</b>16 adult hybrid dogs were randomly divided into normal control group and experiment group. Experimental dogs underwent bilateral mandibular osteodistraction at a rate of 1 min/day. 4 dogs were killed respectively in distraction period, 2 and 8 weeks after completion of 10 days distraction. The bilateral condyles specimens were harvested and examined with histological and immunohistochemical methods.</p><p><b>RESULTS</b>Compared with normal control group, various degrees of irregularities and erosion were found in fibrocartilage of condyle in experiment group, including damage in fibrous layer, hyperplasia layer and proliferative layer and osteogenic activity in cartilage layer. A significant increase of TGF-beta1 expression was also found in experiment groups. TGF-beta1 positive staining was noted in hypertrophic cell, matrix and chondroblast, osteoblast and matrix in osteogenic activity areas. These changes were the most obvious in 2 weeks after completion of distraction.</p><p><b>CONCLUSION</b>Gradual bilateral mandibular distraction at a rate of 1 mm/day brought degenerative changes of condyle, but the changes are reversible.</p>