Endothelial progenitor cells: past, state of the art, and future

Recent evidences suggest that endothelial progenitor cells (EPCs) derived from bone marrow (BM) contribute to de novo vessel formation in adults occurring as physiological and pathological responses. Emerging preclinical trials have shown that EPCs home to sites of neovascularization after ischemic events in limb and myocardium. On the basis of these aspects, EPCs are expected to develop as a key strategy of therapeutic applications for the ischemic organs. Such clinical requirements of EPCs will tentatively accelerate the translational research aiming at the devices to acquire the optimized quality and quantity of EPCs. In this review, we attempt to discuss about biological features of EPCs and speculate on the clinical potential of EPCs for therapeutic neovascularization.     

Plasma appearance and tissue accumulation of non-esterified, free astaxanthin in C57BL/6 mice after oral dosing of a disodium disuccinate diester of astaxanthin (Heptax)

Oral bioavailability of natural and synthetic carotenoids is generally poor in rodents, and this has limited the ability to test these antioxidant compounds in well-defined rodent models of human disease. Various strategies have been employed, with variable success, to increase the percentage of the total oral dose absorbed by the rodent GI tract. In the current study, a novel carotenoid derivative (the disodium disuccinate diester of astaxanthin; Heptax) was administered by oral gavage in a lipophilic emulsion to C57BL/6 mice. Plasma appearance and tissue accumulation of non-esterified, free astaxanthin was studied by HPLC over 72 h after single- and multiple-dose regimens. One-time dosing of Heptax in emulsion at 500 mg/kg resulted in significant appearance of free astaxanthin in plasma (Cmax=0.2 mg/l; 381 nM) and accumulation in solid organs (e.g. liver Cmax=0.9 mg/l; 1735 nM), levels not previously reported after single carotenoid doses in rodents. At each point in the concentration/time curve (AUC), free astaxanthin levels in liver were greater than the corresponding concentration in plasma, suggesting concentrative uptake by the liver. As the ED50 as an antioxidant for non-esterified, free astaxanthin in model systems is approximately 200 nM, the current results suggest that hepatoprotection against oxidative insults may be achieved after a single dose of Heptax in these animals. In humans, where the bioavailability of oral carotenoids ranges from 40 to 60% of the total dose when given in lipophilic vehicle, much smaller oral doses may be utilized for therapeutic benefit in a particular clinical application.     

Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometry

In recent years, consumption of herbal supplements as an alternative to pharmaceutical drug therapy has increased. For example, with the health claims labeling which describes the link between soy-protein and a reduced risk of coronary heart disease (CHD), the consumption of soy and soy-derived phytoestrogens has increased dramatically. That being said, the oral bioavailability of only a few soy phytoestrogens such as Daidzein and Genestein have been previously estimated. In this paper, we present the calculated percent of rat oral bioavailability of five soy-derived phytoestrogens (Genistein, Daidzein, Biochanin A, Coumestrol, and Zearalenone) in male Sprague-Dawley rats. The plasma quantitation required for the bioavailability calculation is performed by using a rapid on-line plasma extraction procedure for the quantitative analysis. To further speed up the analysis the rats were dosed using the 'n-in-one' (cassette) protocol. The rapid on-line extraction/quantitation methodology coupled to the cassette dosing analysis of phytoestrogens is the key point of this paper. The limit of quantitation (LOQ) for each compound was 1-1000 ng/ml with each plasma sample analysis taking less than 2 min. In general the percent oral bioavailability was determined to be between 11 and 28%.     

Eating the evidence? Manduca sexta larvae can not disrupt specific jasmonate induction in Nicotiana attenuata by rapid consumption

As feeding by the tobacco specialist Manduca sexta L. is known to result in significantly higher jasmonate (JA) concentrations in Nicotiana plants than do mechanical simulations of the larval damage, we investigated whether M. sexta, which is known to rapidly consume large quantities of leaf material, can impair this “recognition” response by consuming the leaf tissue before it can respond with amplified JA levels. We report that oral secretions (OS) from M. sexta, but not from the cabbage specialist Pieris rapae, amplified the wound-induced JA response of Nicotiana attenuata Torr. Ex Wats., regardless of larval diet, instar and molting stage, and were still active after boiling and when diluted to 1/1000. The largest JA response occurred within 40 min in tissues adjacent to the OS application site. When 3 mm of leaf tissue immediately adjacent to the OS application site was excised within 40 s, the signal that elicits JA amplification was found to travel rapidly into the leaf, beyond the mandibular reach of the larvae. We conclude that M. sexta is not able to consume the evidence of feeding activity. Received: 16 July 1999 / Accepted: 12 August 1999     

Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma

Cytokinesis, the final step of mitosis, is critical for maintaining the ploidy level of cells. Cytokinesis is a complex, highly regulated process and its failure can lead to genetic instability and apoptosis, contributing to the development of cancer. Human hepatocellular carcinoma is often accompanied by a high frequency of aneuploidy and the DNA ploidy pattern observed in human hepatocellular carcinoma results mostly from impairments in cytokinesis. Many key regulators of cytokinesis are abnormally expressed in human hepatocellular carcinoma, and their expression levels are often correlated with patient prognosis. Moreover, preclinical studies have demonstrated that the inhibition of key cytokinesis regulators can suppress the growth of human hepatocellular carcinoma. Here, we provide an overview of the current understanding of the signaling networks regulating cytokinesis, the key cytokinesis regulators involved in the initiation and development of human hepatocellular carcinoma, and their applications as potential diagnostic and therapeutic biomarkers.     

Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma

Oral cavity squamous cell carcinoma (OSCC), which is frequently associated with poor prognosis and mortality, is a leading cause of cancer‐related death worldwide. Discovery of body fluid accessible biomarkers is needed to improve OSCC screening. To this end, we profiled proteomes of saliva from the healthy volunteers, the individuals with oral potentially malignant disorders (OPMD), and the OSCC patients by means of SDS‐PAGE coupled with LC‐MS/MS. In the control, the OPMD, and the OSCC groups, 958, 845, and 1030 salivary proteins were detected, respectively. With spectral counting‐based label‐free quantification, 22 overexpressed salivary proteins were identified in the OSCC group compared with the healthy controls and the OPMD individuals. Among them, resistin (RETN) was subjected to further validation with an independent cohort using ELISA. The data confirmed that the salivary RETN levels in the OSCC patients were significantly higher than that in the healthy or in the OPMD group. Moreover, the elevated levels of salivary RETN were highly correlated with late‐stage primary tumors, advanced overall stage, and lymph‐node metastasis. Our results not only reveal that profiling of saliva proteome is feasible for discovery of OSCC biomarkers, but also identify RETN as a potential salivary biomarker for OSCC detection.     

CD9在口腔鳞状细胞癌中的表达水平及其临床意义

目的:口腔鳞状细胞癌是一类极易发生局部侵袭和淋巴结转移的恶性肿瘤,CD9蛋白在多种肿瘤的发生发展及侵袭转移过程中起到重要作用,本研究旨在分析CD9蛋白在口腔鳞状细胞癌中的表达水平及其临床意义。方法:收集我院诊断明确的口腔鳞癌肿瘤患者石蜡标本合计80例,通过免疫组化手段对CD9蛋白表达水平进行评价,并根据CD9蛋白的表达水平分组,分析患者的临床病理学特征与CD9蛋白的关系。结果:CD9在正常组织和癌旁组织正常表达,在肿瘤组织中表达率低,其表达水平和口腔鳞癌的分化程度,淋巴结转移及最终分期有相关性(P0.05)。结论:本研究结果揭示,CD9在口腔鳞状细胞癌的发生发展中起到重要作用,CD9蛋白水平的低表达或不表达可能预测着肿瘤具有更明显的恶性生物学行为,并可能成为口腔鳞状细胞癌预后的生物学指标及基因治疗的新靶点。     

第一磨牙窝沟封闭预防龋病的两年临床疗效观察

目的:评估窝沟封闭对预防第一磨牙窝沟龋的2年临床疗效。方法:选择贵阳市花溪区200名7-9岁经家长同意并签署窝沟封闭知情同意书的学生为实验组,进行第一磨牙窝沟封闭;因家长不同意而未进行窝沟封闭的200名同龄学生为对照组,两年内复查两组的龋病发病率和封闭剂的保留情况。结果:实验组窝沟封闭后第一年、第二年第一磨牙龋病的发生率分别为1.50%和1.01%,而对照组分别为4.00%和6.57%,第二年实验组的第一磨牙龋病发病率显著低于对照组,差异有统计学意义(P0.05)。实验组第一年、第二年的封闭剂完全保留率分别是85.5%和80.4%。结论:窝沟封闭作为一项健康干预措施,能有效降低学生的龋病发病率。     

口腔矫正器对错颌畸形患者口腔微生态环境的影响

目的:探讨口腔矫正器对错颌畸形患者口腔微生态环境的影响。方法:选取在我院口腔科进行口腔矫正器治疗的错颌畸形患者48例,分别在矫正治疗前、治疗后1个月、3个月、6个月对其口腔微生物进行培养,观察比较错颌畸形患者在矫正治疗前后口腔微生态环境的变化。结果:1矫正治疗后1个月口腔变形链球菌、乳酸杆菌的检出率分别为16.7%、9.3%,均高于矫正治疗前,且变形链球菌在矫正治疗前后的检出率差异有统计学意义(P0.05)。矫正治疗后3个月、6个月口腔变形链球菌、乳酸杆菌的检出率均较矫正前明显升高,差异有统计学意义(P0.05或P0.01)。2矫正治疗后1个月牙龈卟啉单胞菌、伴放线杆菌、核酸杆菌的检出率分别为14.8%、13.0%和11.1%,均高于矫正治疗,且牙龈卟啉单胞菌、伴放线杆菌在矫正治疗前后的检出率差异有统计学意义(P0.05)。矫正治疗后3个月、6个月牙龈卟啉单胞菌、伴放线杆菌、核酸杆菌的检出率均比矫正前明显升高,差异有统计学意义(P0.05或P0.01)。结论:矫正器的放置破坏口腔微生态环境的平衡,影响牙齿、牙周的健康,应引起临床重视,及早做好预防及干预治疗。     

Fractional killing arises from cell‐to‐cell variability in overcoming a caspase activity threshold

When cells are exposed to death ligands such as TRAIL, a fraction undergoes apoptosis and a fraction survives; if surviving cells are re‐exposed to TRAIL, fractional killing is once again observed. Therapeutic antibodies directed against TRAIL receptors also cause fractional killing, even at saturating concentrations, limiting their effectiveness. Fractional killing arises from cell‐to‐cell fluctuations in protein levels (extrinsic noise), but how this results in a clean bifurcation between life and death remains unclear. In this paper, we identify a threshold in the rate and timing of initiator caspase activation that distinguishes cells that live from those that die; by mapping this threshold, we can predict fractional killing of cells exposed to natural and synthetic agonists alone or in combination with sensitizing drugs such as bortezomib. A phenomenological model of the threshold also quantifies the contributions of two resistance genes (c‐FLIP and Bcl‐2), providing new insight into the control of cell fate by opposing pro‐death and pro‐survival proteins and suggesting new criteria for evaluating the efficacy of therapeutic TRAIL receptor agonists.