Protection of Regenerating Liver After Partial Hepatectomy from Carbon Tetrachloride Hepatotoxicity in Rats: Roles of Mitochondrial Uncoupling Protein 2 and ATP Stores

Uncoupling protein 2 (UCP₂), an inner mitochondrial membrane protein, can limit the generation of reactive oxygen species (ROS) and protect cells from injuries mediated by oxidative stress. We investigated the effect of upregulation of UCP₂ in the regenerating liver 96 h after 68% partial hepatectomy (PH) on the self-protection of regenerating liver against carbon tetrachloride (CCl₄) poisoning. Hepatotoxicity was induced in vivo by administering CCl₄ to rats that had undergone PH. After CCl₄ poisoning, the regenerating liver appeared to have less histological damage and lower serum alanine aminotransferase (ALT) levels. Lower malondialdehyde production and higher glutathione contents were also observed in the regenerating liver compared with the sham-operated liver after CCl₄ poisoning. UCP₂ expression was markedly elevated in the regenerating liver, and further increased after CCl₄ intoxication. Mitochondrial membrane potential and adenosine triphosphate stores maintained higher levels in the regenerating liver than in sham-operated liver after CCl₄ intoxication. The results showed that the regenerating liver exhibited a potent ability to resist CCl₄ intoxication, and the autoprotection of regenerating liver might result from reduction of ROS by UCP₂ and maintenance of higher ATP stores.     

Human parvovirus PARV4 in plasma pools of Chinese origin

Human parvovirus 4 (PARV4) is present in blood and blood products. As the presence and levels of PARV4 in Chinese source plasma pools have never been determined, we implemented real‐time quantitative PCR to investigate the presence of PARV4 in source plasma pools in China. Results showed that 26·15% (51/195) of lots tested positive for PARV4. The amounts of DNA ranged from 2·83 × 10³ copies/ml to 2·35×10⁷ copies/ml plasma. The high level of PARV4 in plasma pools may pose a potential risk to recipients. Further studies on the pathogenesis of PARV4 are urgently required.     

Plasma level of lipopolysaccharide-binding protein is indicative of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Acute graft-versus-host disease (aGVHD) is the major cause of non-relapse mortality following allogeneic hematopoietic stem cell transplantation. To date, there are no consensus specific plasma biomarkers for aGVHD. We recently identified several candidates differentially expressed in aGVHD patients. Here, we have validated one such candidate: lipopolysaccharide-binding protein (LBP). We detected plasma LBP level by ELISA in 73 patients and performed correlation analysis with the progression and severity of aGVHD. We found that plasma LBP level increased during the period of aGVHD and decreased markedly as aGVHD was resolved. LBP level in patients with moderate aGVHD (25-50 % skin rash area of grade 1 and grade 2) was higher than in patients with no, little (skin rash area <25 % of grade 1), or severe aGVHD (grade 3-4). Higher LBP level indicated higher probability of aGVHD. Multivariate analysis showed that LBP level above 15000 ng/ml was significantly associated with an increased risk of aGVHD (HR 2.43; 95 % CI 1.29-4.58; P = 0.006). If LBP level exceeded 15000 ng/ml at d7 and d14 after HSCT, the subsequent probability of aGVHD increased markedly, especially at the time point of d14. There was no correlation between LBP level and the site of aGVHD. In conclusion, our study demonstrated that an elevated LBP level of >15000 ng/ml may serve as a biomarker for the prediction and monitoring of aGVHD.     

Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population

Purpose

To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.

Methods

We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.

Results

We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p?=?0.033, aOR?=?0.742, 95%CI?=?0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p?=?0.037, aOR?=?0.771, 95%CI?=?0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p?=?0.021, aOR?=?0.529, 95%CI?=?0.307–0.910) and TMN stage (p?=?0.021, aOR?=?0.532, 95%CI?=?0.311–0.908), respectively.

Conclusions

Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.     

Association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease

Enterovirus 71 (EV71) is one of the common causative agents of hand, foot and mouth disease (HFMD), and is associated with several outbreaks with neurological complications including encephalitis. This study investigated the polymorphisms of interferon gamma (IFN-γ)+874 T/A and interleukin 10 (IL-10)-1082 G/A in 65 Chinese patients with EV71 encephalitis and 113 Chinese HFMD patients without complications. The polymorphisms of IFN-γ+874 T/A and IL-10-1082 G/A were determined by polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) and PCR-sequence-specific primer (SSP) analysis, respectively. The IFN-γ + 874 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (76.2%) compared with HFMD patients without complications (61.1%, p < 0.01). Similarly, the IL-10 - 1082 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (86.2%) compared with HFMD patients without complications (77.0%, p < 0.05). IFN-γ + 874 A and IL-10 - 1082 A alleles are associated with susceptibility to EV71 encephalitis in Chinese patients.     

Reduced Popdc3 expression correlates with high risk and poor survival in patients with gastric cancer

AIM: To investigate the expression of Popeye domain containing 3 (Popdc3) and its correlation with clinicopathological features and prognosis of gastric cancer.METHODS: The method of immunohistochemistry was used to investigate the expression of Popdc3 in 306 cases of human gastric cancer and 84 noncancerous gastric tissues. Simultaneously, the relationship between Popdc3 expression and the survival of the patients was retrospectively analyzed.RESULTS: Popdc3 was detected in 72 (85.71%) of 84 human nontumor mucosa. High expression of Popdc3 protein was detected in 78 (25.49%) of 306 human gastric cancer cases, and low expression was detected in 228 (74.51%). Low expression of Popdc3 correlated with depth of invasion (P < 0.0001), regional lymph nodes (P < 0.0001) and distant metastasis (P = 0.02), and tumor, nodes, metastasis (TNM) stages (P < 0.0001). On multivariate analysis, only the patient’s gender, regional lymph node metastasis, distant metastasis, TNM stages, and the expression of Popdc3 were independent prognostic factors in patients with gastric cancer. The Kaplan-Meier plot showed that low Popdc3 expression had a much more significant effect on the survival of those patients with early-stage tumors (χ² = 104.741, P < 0.0001), with a > 51.9% reduction in the three-year survival compared with high Popdc3 expression. In late stages, the difference was also significant (χ² = 5.930, P = 0.015), with a 32.6% reduction in the three-year survival.CONCLUSION: Reduced expression of Popdc3 may play a significant role in the carcinogenesis and progression of gastric cancer. Popdc3 may be an independent prognostic factor.     

Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Abstract: Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti‐angiogenic capability is urgent in clinical practice. In this study, a co‐culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC‐1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co‐cultured with PANC‐1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC‐1 cells. In addition, the VEGF mRNA expression was also down‐regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co‐culturing them with PANC‐1 cells; this was associated with a suppression of VEGF expression in PANC‐1 cells.     

Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

AIM:To investigate the relationship between donor liver cold preservation,lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation.METHODS:Liver transplantation models were estab-lished using male Wistar rats.Donor livers were pre-served in University of Wisconsin solution at 4 ℃ for different lengths of time.The effect of ammonium pyr-rolidinedithiocarbamate (PDTC) on ALI was also detect-ed.All samples were harvested after 3 h reperfusion.The severity of ALI was evaluated by lung weight/body weight ratio,lung histopathological score,serum nitric oxide (NO) and endothelin (ET)-1 levels,lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels.Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography.RESULTS:With extended donor liver cold preservation time (CPT),lung histopathological scores,serum ET-1 levels,lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21,P 0.001;343.59 ± 53.97 vs 141.53 ± 48.48,P 0.001;0.00687 ± 0.00037 vs 0.00557 ± 0.00056,P 0.001;17.5 ± 3.0 vs 1.3 ± 0.3,P 0.001;10.8 ± 2.3 vs 1.8 ± 0.4,P 0.001),but se-rum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18,P 0.001).The expression of lung phos-phatidylcholine (PC),phosphatidylethanolamine (PE),phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was 120 min,and decreased when CPT was 180 min (PC:1318.89 ± 54.79 vs 1011.18 ± 59.99,P 0.001;PE:1504.45 ± 119.96 vs 1340.80 ± 76.39,P=0.0019;PI:201.23 ± 34.82 vs 185.88 ± 17.04,P=0.2265;PS:300.43 ± 32.95 vs 286.55 ± 55.55,P=0.5054).All these ALI-associated indexes could be partially reversed by PDTC treatment.CONCLUSION:Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decom-pensation stage,and some antioxidants (e.g.,PDTC) may reverse the pathological process partially.     

经颅多普勒脉动指数与病理改变相关性的实验研究

目的 探讨经颅多普勒(TCD)脉动指数(PI)与病理改变的相关性.方法 采用24只健康雄性新西兰大白兔作实验动物,对其进行高脂饲料喂养及一侧肾动脉狭窄致高血压处理制备动脉粥样硬化模型.分别在实验前、实验第8周、第16周用TCD对颈内动脉及大脑中动脉进行血流速度的检测,然后进行相关病理改变检测.结果 颈内动脉在动脉粥样硬化过程中PI值逐渐升高,当PI值>0.86(P<0.05)时,病理切片可观察到内皮不完整,有脱落,内弹力层断裂,平滑肌细胞增加,管腔明显变小;大脑中动脉在动脉粥样硬化过程中PI值的改变在各检测点均无统计学意义,病理切片没有明显改变.结论 在脑动脉硬化进程中,PI值的改变与动脉的硬化程度及病理变化有较好的相关性.     

NOD2/CARD15基因R702W、G908R及L1007fs多态性与广西壮族人群炎症性肠病的相关性

目的:探讨我国广西壮族人群NOD2/CARD15基因R702W、G908R及L1007fs的遗传多态性与炎症性肠病的相关性.方法:分别收集2007-02/2010-10在广西地区无亲缘关系的壮族(n=70)和汉族(n=76)IBD患者及壮族(n=80)和汉族(n=84)正常对照者的肠黏膜组织.采用酚氯仿法提取各组织样本DNA,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法对NOD2/CARD15基因R702W、G908R及L1007fs进行检测,统计基因型及等位基因频率,分析上述3个多态性位点与广西壮族人群炎症性肠病的相关性.结果:广西壮族和汉族IBD患者与正常对照者均未发现NOD2/CARD15基因R702W、G908R及L1007fs突变型基因型,所有多态性位点上的基因型全部为野生型纯合子,其基因型频率和等位基因频率分布在IBD患者和正常对照者中差异无统计学意义(P>0.05).结论:NOD2/CARD15基因R702W、G908R及L1007fs多态性与广西壮族人群炎症性肠病无明显相关性.