Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响

目的:研究滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响。方法:将广州市花都区妇幼保健院收治的100例甲状腺功能亢进症阴虚火旺证患者分成观察组和对照组。对照组:给患者使用常规药物治疗;观察组:在对照组的基础上,给予滋阴清热方治疗。干预后,比较两组患者的临床疗效、血浆内皮素-1(Endothelin,ET)、炎症因子[白介素-2(Interleukin-2,IL-2)、白介素-8(Interleukin-8,IL-8)]及肿瘤坏死因子(Tumour Necrosis Factor-α,TNF-α)和免疫功能(CD3^+、CD4^+、CD8^+及CD4^+/CD8^+)。结果:干预前,两组患者IL-2、IL-8及TNF-α无变化,差异无统计学意义(P>0.05);干预后,观察组患者的IL-2比对照组高,且对照组的IL-8及TNF-α比观察组的高,P<0.05,差异有统计学意义;干预前,两组患者的CD3^+、CD4^+、CD8^+及CD4^+/CD8^+与ET无变化;干预后,观察组的CD3^+、CD4^+、CD8+及CD4^+/CD8^+比对照组高,P <0.05,差异有统计学意义,且观察组的ET低于对照组且观察组总有效率明显高于对照组。结论:滋阴清热方治疗降低了血浆内皮素-1,减少炎症的出现,提高免疫功能。     

高脂血症时血清二乙基对硝基苯磷酸酯酶活性的变化

目的 :研究tritonWR 13 3 9致小鼠高脂血症时血清二乙基对硝基苯磷酸酯酶 (ParaoxonaseI ,PON 1)活性的变化及PON 1活性与血浆脂质含量之间的关系。方法 :在小鼠尾静脉注射tritonWR13 3 9后的 3h ,6h ,12h ,2 4h ,48h ,72h ,眼球摘除术取血 ,用酶标法测定小鼠血浆总胆固醇 (TC) ,甘油三酯 (TG ) ,高密度脂蛋白 -胆固醇 (HDL -C) ,载脂蛋白AI (ApoAI) ,载脂蛋白B (ApoB含量 ) ,并计算出ApoAI/ApoB ,HDL -C/TC比值 ,用分光光度计法测定PONI活性。结果 :TritonWR 13 3 9尾静脉注射后 3h ,小鼠血浆TC和TG含量即急剧增高 ,与对照组相比 ,P <0 .0 1,分别在注射后 2 4h和 3h达到峰值 ,随后逐渐下降 ,其中血浆TG含量在注射后 48h即恢复正常水平。tritonWR13 3 9尾静脉注射后 3h ,小鼠血浆HDL -C和ApoB含量急剧增高 ,与对照组相比 ,P <0 .0 5,分别在注射后 2 4h和 6h达到峰值 ,随后逐渐下降 ,分别在注射后 48h和 72h恢复正常水平。tritonWR13 3 9尾静脉注射后 3h ,小鼠血浆ApoAI含量即急剧降低 ,与对照组相比 ,P <0 .0 5,随后逐渐增高 ,在注射后 6h即恢复正常水平。tritonWR 13 3 9尾静脉注射后 3h ,小鼠血浆ApoAI/ApoB和HDL-C/TC比值减少 ,与对照组相比 ,P <0 .0 1,随后逐渐增高 ,其中ApoAI/ApoB比值在 72h恢复     

多发性骨髓瘤患者血浆尿激酶型纤溶酶原激活物及其可溶性受体的检测与临床意义

目的 :研究多发性骨髓瘤 ( MM)患者血浆尿激酶型纤溶酶原激活物 ( u- PA )及其可溶性受体 ( su PAR )的水平变化 ,并探讨其临床意义。方法 :用 ELISA法检测 34例 MM患者血浆 u- PA及 su PA R的浓度 ,同时观察其中6例 MM患者化疗前后血浆 u- PA及 su PAR的浓度变化。结果 :MM患者血浆 u- PA及 su PA R水平均明显高于正常对照组 ,其中进展期 MM患者血浆 u- PA及 su PAR水平明显高于正常对照组和稳定期 MM患者 ( P <0 .0 1) ,而稳定期 MM患者血浆 u- PA及 su PA R水平与正常对照组无显著性差异 ( P>0 .0 5)。 6例 MM患者化疗后血浆 u- PA及 su PA R水平 ,明显低于化疗前血浆 u- PA及 su PAR水平 ( P<0 .0 5)。骨髓涂片瘤细胞比例 >2 0 %的 MM患者血浆 u- PA及 su PA R水平 ,明显高于瘤细胞比例≤ 2 0 % M M患者 ( P<0 .0 5;P<0 .0 1)。M M患者血浆 u- PA及su PA R水平均与骨髓瘤细胞百分比及血清球蛋白呈正相关 ,而与血清白蛋白呈负相关。结论 :血浆 u- PA及 su PA R水平升高可能与多发性骨髓瘤的发生、发展有密切关系 ;其水平可作为临床分期、判断疗效、了解疾病进展情况及预后的一个重要指标。     

Human khat (Catha edulis) chewers have elevated plasma leptin and nonesterified fatty acids

In this study, the effect of regular khat (Catha edulis Forsk) chewing (200 and 400 g) in humans on plasma leptin, nonesterified fatty acid, triacyglycerol, and total cholesterol levels was investigated. The results presented show that khat chewing increases plasma leptin concentration particularly in individuals who chew 400 g of khat leaves. The significance of increased plasma leptin is in explaining the underlying mechanism of the observed effects associated with khat chewing such as loss of appetite, decreased body weight, and hyperthermia. The decreased body weight was evident from the significantly lower body mass index of the khat leaves chewers group as compared to the non–khat leaves chewers group (control). Moreover, like leptin, the plasma levels of nonesterified fatty acids were significantly higher in those chewing 400 g of khat leaves. On the other hand, the plasma levels of triacylglycerol were significantly lower in the 2 khat-chewers groups (200 and 400 g of khat leaves), whereas plasma cholesterol levels were not affected by the 2 levels of khat leaves used in this study. The significance of these results may suggest that khat leaves may contain a component(s) that has the ability to reduce body weight via decreasing appetite.