Nitric oxide donor,NOC7, reveals dose dependently and cGMP pathway independently biphasic effects on contractile force of isolated rat heart after global ischemia

Purpose: Our purpose was to investigate whether the 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), an ideal NO donor was dose dependently and cGMP-independent in restored cardiac function after global ischemia in an isolated rat heart model. Methods: Langendorff preparations of an isolated rat heart model were established. Isolated rat hearts (n = 40) were randomly divided into 5 groups (ischemic control group, NOC7 groups and NOC7+NS2028 groups). All groups were subjected to 35 min global ischemia, followed by 30 min reperfusion with Krebs-Henseleit bicarbonate buffer (KHB), and NOC7, NOC7+NS2028 at 2 and 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flows were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA). Results: 30 min of global ischemia increased LVDP to 121.9±11.5% at 35 min of reperfusion of 2 μM NOC7 group and 2 μM NOC7 associated with NS2028 group from the ischemic control group (P < 0.05). While in 200 μM NOC7 group and 200 μM NOC7 associated with NS2028 group, the LVDP value only slightly reduced, resulting in a value of only 45.3±10.4% and 35.3±6.0% of baseline (P > 0.05). Conclusion: NOC7 has biphasic effect on isolated rat heart after ischemia and reperfusion myocardial contractility. This biphasic effect shows neither concentration-dependent nor the cGMP-dependent characteristics.     

ALEX1 may be a novel biomarker for human cervical squamous cell carcinoma

The armadillo repeat proteins were first found in armadillo gene of Drosophila. Since then a number of proteins containing armadillo repeats have been noticed and studied. These proteins that consist of 6 to 13 armadillo repeat domains are classified as family of armadillo repeat proteins. Recently, several studies indicated that armadillo repeat family of proteins play an important role in the tumorigenesis and maintenance of tissue integrity. ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues. Several studies have found that ALEX1 protein lost in tumors that originated in epithelial tissues. We evaluated the ALEX1 protein expression in 53 cervical cancers and in 53 non-cancerous cervical tissues from patients and adjacent non-cancerous tissues using immunohistochemistry Results: ALEX1 protein expression is significantly increased in 53 cervical cancers tissues compared with non-cancerous tissues. We found, for the first time, that ALEX1 protein expression in cervical cancers tissues is higher than non-cancerous tissues. It is suggested that the ALEX1 protein is associated with tumorigenesis in cervical cancer and we speculate that the ALEX1 may plays a role as an oncogene in cervical cancer. Moreover, ALEX1 may serve as a novel potential diagnostic biomarker in identifying cervical cancer.     

Down-regulation of PAX6 by promoter methylation is associated with poor prognosis in non small cell lung cancer

Background: Promoter methylation is an alternative mechanism of gene silencing in human tumorigenesis. Although a number of methylated genes have been found in non small cell lung cancer (NSCLC), useful methylation markers for early prognostic evaluation of NSCLC remain largely unknown. Methods: Using methylation-specific PCR (MSP), we examined promoter methylation status of PAX6 gene, and explored their association with clinical features in NSCLC via chi-square test. NSCLC patient survival was assessed by Kaplan-Meier analyses and a Cox proportional hazard model was employed for multivariate analyses. Results: The methylation level of PAX6 gene was higher in tumor tissues than that in normal tissues. In addition, PAX6 promoter methylation showed a very significant correlation with differentiation (P = 0.002), distant metastasis (P = 0.024), and TNM stage (P = 0.002). PAX6 gene promoter hyper-methylation was found to be significantly associated with poor overall survival (P = 0.018) and to serve as an independent marker for prognosis using multivariate Cox regression analysis (HR: 2.254, 95% CI: 1.088-4.667, P = 0.029). Conclusion: We found that PAX6 gene was specifically methylated in NSCLC, and demonstrated the effect of promoter methylation of PAX6 gene on clinical outcome in NSCLC, indicating the methylated PAX6 may be useful biomarkers for prognostic evaluation in NSCLC.     

类风湿性骨病与牙周炎的病因机制相关性研究进展

类风湿性骨性疾病大体包括类风湿性关节炎和强直性脊柱炎。这两种类风湿性骨病与牙周炎都是自身免疫相关性疾病,牙周炎人群中类风湿性骨病的发病率增加,类风湿性骨病患者牙周炎发病率同样增高。究其原因,牙周炎与类风湿性骨病在病因机制方面存在共同之处。本文就类风湿性骨病与牙周炎患病与治疗相关性,造成发病部位炎性表现和骨质改变的原因、机理进行综述。希望以此增加多学科的联合以及对牙周病的深入研究提供理论依据。     

早期穴位按摩配合电动吸乳促进母乳喂养的效果研究

目的 探讨早期穴位按摩配合电动吸乳对母乳喂养的影响.方法 选择100例产妇 ,随机分为观察组(50例)和对照组(50例) ,对照组采用常规乳房护理 ,观察组在此基础上进行早期穴位按摩配合电动吸乳.记录两组产妇泌乳始动时间 ;产后24h、48h、72h的泌乳量 ;产后2d、3d、4d的乳房肿胀硬度以及产后第5天纯母乳喂养率的情况.结果 观察组产妇泌乳始动时间早于对照组( P<0 .05 );观察组产后24 h、48 h、72 h的泌乳量均多于对照组(P<0 .05);观察组产后第5天纯母乳喂养率明显高于对照组(P<0 .05).结论 基于常规乳房护理的早期穴位按摩配合电动吸乳可增加乳汁分泌 ,促进母乳喂养成功.     

SOD2基因多态性与突发性耳聋的遗传易感性研究

目的：探讨人线粒体超氧化物歧化酶2(mitochondrial superoxide dismutase 2, SOD2)基因多态性与云南地区突发性耳聋(idiopathic sensorineural hearing loss, SSNHL)患者遗传易感性的关系。方法采用病例-对照研究,选取78例(男35,女43)突发性耳聋患者和与之性别、年龄相匹配的85例(男39,女46)对照群体,对 SOD2基因的3个标签 SNP 位点(rs5746136、 rs2842960、 rs4880)进行基因分型,统计并分析了基因频率和基因型频率分布与突发性耳聋的遗传易感性的关系。结果在 rs5746136位点(OR ＝2.136,95％ CI ＝1.147~3.978, P ＝0.016)上的 A/ G 基因型可能是中国突发性耳聋患者的危险基因型,而 rs2842960和 rs4880则和中国突发性耳聋患者无相关性;结论 SOD2基因多态位点 rs5746136 A/ G 基因型可能增加突发性耳聋患者的风险,可以作为预测 SSNHL 患者发病危险及早期防治的的遗传标记。     

Suppression of human hepatocellular cancer cell proliferation by Brucea javanica oil-loaded liposomes via induction of apoptosis

Introduction

Hepatocellular carcinoma (HCC) is a type of malignancy with high incidence and poor prognosis. Brucea javanica is extracted from Simaroubaceae plants. It is found to have low toxicity but high anti-cancer efficiency. The aim of this study is to determine the effects of Brucea javanica oil-loaded liposomes (BJOL) on human hepatocellular cancer cell line HepG2. The related molecular mechanisms were determined.

Material and methods

Morphologic changes of HepG2 cells were observed by transmission electron microscope after treatment with BJOL in vitro. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after cell treatment with different doses of BJOL. Flow cytometry was performed. Nude mice were divided into 4 groups randomly and treated with different doses of BJOL. The apoptosis hepatocellular carcinoma was detected by TUNEL.

Results

Proliferation of HepG2 was inhibited significantly by BJOL in a dose-dependent manner (2.5 mg/l or 5 mg/l). Compared with the animal models treated with the negative control, the animal models in the BJOL group had higher weight and lower metastasis rates (p < 0.01). The rate of apoptosis in hepatocellular carcinoma tissue of the BJOL groups was increased when compared with the control group (p < 0.05).

Conclusions

Brucea javanica oil-loaded liposomes inhibits proliferation of HepG2. The effect appears to be dose-dependent, possibly by inducing apoptosis of cancer cells.     

Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis

OBJECTIVES:

To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness.

METHODS:

A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry.

RESULTS:

The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera.

CONCLUSION:

This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future.     

Calcium signaling is implicated in the diffuse axonal injury of brain stem

Evaluating diffuse axonal injury (DAI) remains challenging in clinical sciences since the physiopathologic mechanism of DAI is still unclear. The calcium overload in the axoplasm is considered to be crucial for secondary axonal injury. The present study use calcium channel blocker, nimodipine, to explore the influence of Ca²⁺ in the pathogenesis of rat DAI. In the DAI group, the expressions of β-APP and NF-L in axons were increased from 12 to 72 h. The ultrastructural observation indicated the axon and vessel injury appeared at 12 h post-injury and severely aggravated from 24 to 72 h. The expression of vWF and brain water content was increased at 12 h after injury and further increased at 24 h. Nimodipine decreased the expression of β-APP, NF-L and vWF, and also attenuated the ultrastructural damage of vascular wall and axons. Furthermore, Ca-dependent enzyme, the calcineurin activity were increased in DAI and nimodipine suppressed the activity of calcineurins (CaN). However, the amount of CaN expression was not changed. Our results showed that disturbances of axonal calcium homeostasis play an important role in the secondary damage of the axon, neuron and capillary vessel which may be related with activating CaN during the acute phase of DAI. Nimodipine can alleviate the secondary damage by suppressing the calcineurin activity.     

Gene polymorphism of IL-6 and MMP-3 decreases passive range of motion after rotator cuff repair

Objectives: Post-operative stiffness is common after rotator cuff repair, given the difference in susceptibility and severity, the genetic factors may be involved. Interleukin 6 (IL-6) and Matrix metalloproteinases 3 (MMP-3) were previous found as key cytokines in the pathologies of adhesive capsulitis. The present study aims to investigate whether variants within the IL-6 and MMP-3 gene contributed to post-operative stiffness in a Chinese Han population. Methods: A total of 188 patients diagnosed with rotator cuff tears treated with mini-open surgery were enrolled in this study, among which 87 patients were diagnosed as post-operative stiffness and the remaining 101 patients as controls. All subjects were genotyped for IL-6 and MMP-3 SNPs. Results: The rs1800796 of IL-6 and rs679620 of MMP-3 were found significantly associated with increased susceptibility and severity of post-operative stiffness. Conclusion: The rs1800796 SNP of IL-6 and rs650108 SNP of MMP-3 were associated with increased risk of post-operative stiffness susceptibility and severity. This finding can be used in guiding the rehabilitation procedure after rotator cuff surgery, in another word, those with the genetic susceptibility factors should receive a more radical rehabilitation procedure and those without the susceptibility factors can be more conservative.