Effect of vascular cell adhesion molecule 1 on fibroblasts in human eosinophilic chronic rhinosinusitis

The pathogenesis of eosinophilic chronic rhinosinusitis (ECRS) is still unclear. Paranasal mucosa inflammation is thought to be related to eosinophilic infiltration. This infiltration seems to induce changes in the expression of cell adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1). The E-cadherin-beta-catenin complex maintains the integrity of the epithelium. Downregulation of beta-catenin and E-cadherin is a pivotal factor for progressive cell growth. This study aimed to assess which cytokines regulate the expression of the adhesion molecule E-cadherin and the multi-functional protein beta-catenin, which plays a key role in cadherin-mediated anchoring in ECRS. Cultured ECRS specimens were incubated with human VCAM-1. After a period of up to 72 h, expression of E-cadherin and beta-catenin was determined using cytokine immunoassay and immunohistochemistry. In ECRS, significant increases in E-cadherin expression were found in fibroblast cell cultures. Stimulation with VCAM-1 did not produce a significant alteration in the expression of the adherens junction protein beta-catenin. In addition, VCAM-1 did not decrease the levels of membrane staining for adherens junction proteins. The selective increase in E-cadherin expression in eosinophilic fibroblast cultures might be explained by a higher concentration of the Th2-type cytokines in these cultures. The tissue remodelling observed during chronic eosinophilic inflammation offers new insight into the pathogenesis of ECRS.     

成体干细胞的可塑性

继1999年和2000年连续两年被列为年度"人类十大科技进展"后,有关干细胞研究于2007年被再次列为年度十大科学突破之一.干细胞由于具有自我复制、高度增殖和多向分化潜能等特点,已经成为组织细胞发育分化研究、临床医疗应用等领域的重要材料与产品.     

Cell sheet engineering for the injured heart

Myocardial infarction and subsequent heart failure are a leading cause of morbidity and mortality. Tissue engineering is emerging as promising alternative approach to treat these kinds of diseases. However, conventional applications using biodegradable scaffolds have disadvantages, such as biocompatibility, biodegradability, and cytotoxicity, and this limits its efficacy. Cell sheet engineering without artificial scaffolds to form new myocardial constructs avoids the shortcomings of traditional tissue engineering approaches using scaffolds. We hypothesize that cell sheet engineering may be a promising strategy for cardiac tissue reconstruction.     

Cell delivery in cardiac regenerative therapy

There is a growing interest in the clinical application of stem cells as a novel therapeutic approach for treatment of myocardial infarction and prevention of subsequent heart failure. Transplanted stem cells improve cardiac functions through multiple mechanisms, which include but are not limited to promoting angiogenesis, replacing dead cardiomyocytes, modulating cardiac remodeling. Most of the results obtained so far are exciting and very promising, spawning an increasing number of clinical trials recently. However, many problems still remain to be resolved such as the best delivery method for transplantation of cells to the injured myocardium and the issue of how to optimize the delivery of targeted cells is of exceptional clinical relevance. In this review, we focus on the different delivery strategies in cardiac regenerative therapy, as well as provide a brief overview of current clinical trials utilizing cell-based therapy in patients with ischemic heart disease.     

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single-nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P-value=1.45 × 10(-12)), rs12603708 in the intron (combined P-value=1.82 × 10(-8)) and rs3751987 at ～65?kb downstream of the 5'-UTR region of TNFRSF13B (combined P-value=3.67 × 10(-9)). Additionally, smoking was identified to be associated with IgG level in both stages (P<0.001), but there was no significant interaction between smoking and the identified SNPs (P>0.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B.     

ObesiTV: how television is influencing the obesity epidemic

Obesity is a major public health concern in the United States. Over the last several decades, the prevalence of obesity among both adults and children has grown at an alarming rate and is now reaching epidemic proportions. The increase in obesity has been associated with rises in a host of other chronic conditions including cardiovascular disease, type 2 diabetes, and some cancers. While the causes of obesity are multifaceted, there is growing evidence that television viewing is a major contributor. Results of numerous studies indicate a direct association between time spent watching television and body weight. Possible explanations for this relationship include: 1) watching television acts as a sedentary replacement for physical activity; 2) food advertisements for nutrient-poor, high-calorie foods stimulate food intake; and 3) television viewing is associated with "mindless" eating. In addition to decreasing physical activity and increasing the consumption of highly palatable foods, television viewing can also promote weight gain in indirect ways, such as through the use of targeted product placements in television shows; by influencing social perceptions of body image; and airing programs that portray cooking, eating and losing weight as entertainment. This paper will provide an interdisciplinary review of the direct and indirect ways in which television influences the obesity epidemic, and conclude with ways in which the negative impact of television on obesity could be reduced.     

Mitochondrial tRNA mutations are associated with maternally inherited hypertension in two Han Chinese pedigrees

We report here the clinical, genetic, molecular, and biochemical evaluations in two Han Chinese families with maternally inherited hypertension. Fourteen of 20 adult matrilineal relatives of these families exhibited a wide range of severity in hypertension, while none of offspring of affected fathers had hypertension. The age-at-onset of hypertension in matrilineal relatives varied from 37 years to 83 years, with an average of 55 and 66 years, respectively. Mutational analysis of their mitochondrial genomes identified the m.4353T>C mutation in the tRNA, in conjunction with the known m.593C>T mutation in the tRNA(Phe) and m.5553C>T mutation in the tRNA(Trp). Northern analysis revealed that m.4353T>C, m.593C>T and m.5553C>T mutations caused ～66%, 65%, and 12% reductions in the steady-state level of tRNA(Gln), tRNA(Phe) and tRNA(Trp), respectively. An in vivo protein labeling analysis showed ～35% reduction in the rate of mitochondrial translation in cells carrying these tRNA mutations. Impaired mitochondrial translation is apparently a primary contributor to the reduced rates of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or N,N,N',N'-tetramethyl-p-phenylenediamine/ascorbate-promoted respiration and the increasing level of reactive oxygen species in the cells carrying these mtDNA mutations. These data demonstrate that mitochondrial dysfunction caused by mitochondrial tRNA mutations is associated with essential hypertension in these families.     

Effects of Efflux Pump Inhibitors on Erythromycin, Ciprofloxacin, and Tetracycline Resistance in Campylobacter spp. Isolates

The aim was to assess the potency of the efflux pump inhibitors (EPIs) phenylalanine-arginine ?-naphthylamide (PA?N) and 1-(1-naphthylmethyl)-piperazine (NMP) and the putative natural EPI phenolic (-)-epigallocatechin gallate (EGCG) for the reversal of erythromycin, ciprofloxacin, and tetracycline resistance in Campylobacter jejuni and Campylobacter coli isolates. We investigated target mutations and resistant genes involved in erythromycin and tetracycline resistance and determined the roles of the bacterial drug efflux systems (cmeB, cmeF, and cmeR) in antimicrobial resistance. Our data show that most of the high-level erythromycin resistance and all of the tetracycline resistance can be explained through mutations in 23S rRNA and the presence of the tetO gene, respectively. The EPIs show the ability to partly reverse drug resistance in these Campylobacter isolates. Based on a fourfold or greater reduction in the erythromycin minimal inhibitory concentration (MIC), PA?N and NMP had clear effects in almost of all of the isolates tested. PA?N had a highly selective action on the ciprofloxacin and tetracycline MICs. Inactivation of cmeB increased susceptibility to all of the antimicrobials tested, whereas inactivation of cmeF and cmeR had no effects. A notable decrease in resistance to erythromycin and ciprofloxacin in the presence of subinhibitory concentrations of EGCG demonstrates the resistance-modifying activities of this natural EPI, and indicates its potential use in the control of Campylobacter spp. in the food chain.     

基于预扫描正则化与稀疏约束重建的低剂量CT灌注成像

CT灌注成像中患者会受到长时间的X线照射,在灌注前预先扫描一幅正常剂量图像,在后续灌注过程中进行低剂量采集,将所获低剂量图像与参考图像做减影并进行滤波处理以获得灌注信息,然后叠加到正常剂量图像中,可以非常显著地降低CT灌注成像中辐射剂量,然而,当剂量非常低的时候,重建图像会受到噪声与伪影干扰。本文基于类似的预扫描正则化数据采集方案,分别进行正常剂量和低剂量预扫描,然后利用相同的低剂量进行后续灌注过程的扫描,将所采集低剂量数据与预扫描的低剂量数据在投影域作差,然后在重建中引入稀疏性约束,以获得更准确的灌注信息重建,重建后的灌注信息最后同样叠加到正常剂量图像中。本文采用一套人脑CT灌注图像进行模拟实验,结果表明在同样剂量下,本文所提新方法重建结果所包含的灌注信息更准确,时间衰减曲线与正常剂量情况的吻合度更高,而且平均过渡时间可重复性好。     

Vitamins at physiological levels cause oxidation to the DNA nucleoside deoxyguanosine and to DNA--alone or in synergism with metals

Vitamins with antioxidant properties have the ability to act as pro-oxidants, inducing oxidative damage and oxidative stress as opposed to preventing it. While vitamin supplements are commonly consumed, the scientific evidence for their health beneficial effects is inconclusive. In fact, even harmful effects have been reported. The present study aimed to investigate and compare pro-oxidant properties of different antioxidants and vitamins commonly found in dietary supplements, at concentrations of physiological relevance, alone or in combination with metals also found in supplements. Focus was on damages related to DNA. The vitamins' chemical oxidation potencies were studied by measuring the amount of the oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formed from the DNA nucleoside deoxyguanosine (dG) after vitamin exposure, using a high-performance liquid chromatography system with electrochemical and ultraviolet detection. To study the vitamins' ability to cause DNA damage to cultured cells, promyelocytic leukemia cells (HL-60) were exposed to vitamins, and strand breaks, alkali-labile sites and oxidative DNA lesions, i.e. formamido pyrimidine DNA glycosylase-sensitive sites, were detected using the comet assay. Vitamins A and C chemically induced oxidation of dG, alone and in synergism with iron or copper, whereas only vitamin C and copper induced DNA damage in cultured cells. Contrary, vitamins B1, B2, B3, B6 and B12, β-carotene, folic acid, α-tocopherol, δ-tocopherol or γ-tocopherol did not induce oxidative damage to dG, while lycopene induced a weak dose-response increase. Taken together, vitamin C and copper stood out with the strongest oxidative potency, which is of potential concern since both substances are commonly found in multivitamins.