基于新靶点的抗真菌药物研究进展

侵袭性真菌感染的发病率正逐年上升。现有抗真菌药物由于抗菌谱有限、副作用大等原因,致使临床应用受限。因此,基于新靶点的抗真菌药物成为治疗真菌感染的迫切需要。近年来,抗真菌药物研究取得较大进展。其中,抑制真菌细胞壁合成的药物（如E1210和D11?2040）、抑制蛋白激酶或蛋白磷酸酶信号通路的药物（如KP?372?1、17?AAG、Mycograb）、靶向真菌毒力因子的单克隆抗体（如C7、213 Bi?18B7、188 Re?18B7）、激活宿主免疫系统的疫苗[如PEV7和β?（ Man）3?Fba?TT]等,正引起人们的关注。     

Dietary supplementation with high dose of epigallocatechin-3-gallate promotes inflammatory response in mice

Epigallocatechin-3-gallate (EGCG) from green tea has been indicated to have anti-inflammatory activity. However, most of the evidence is in vitro studies in which EGCG is often added at levels unachievable by oral intake. With few exceptions, in vivo studies along this line have been conducted in animal models of diseases, and the results are inconclusive. In this study, we fed C57BL/6 mice a diet containing 0%, 0.15%, 0.3% or 1% (w/w) EGCG for 6 weeks. Contrary to the assumption that EGCG would reduce inflammatory response, mice fed 0.15% and 0.3% EGCG diet exhibited no change while those fed 1% EGCG diet produced more proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1β and lipid inflammatory mediator prostaglandin E(2) in their splenocytes and macrophages (MΦ) and less IL-4 in splenocytes. Spleens from the mice fed 1% EGCG diet also had higher proportions of regulatory T cells, MΦ, natural killer (NK) cells and NKT cells compared to those from mice fed the other diets. These results suggest that high intake of EGCG may induce a proinflammatory response, and this change may be associated with a disturbed homeostasis of immune cells involving changes in both function and number of specific immune cell populations. While the mechanisms and clinical significance for this effect of EGCG remain to be investigated further, these data suggest the need for defining accurate EGCG dose limits to induce an anti-inflammatory effect since current data indicate that higher doses would produce an inflammatory response.     

Morphology and mechanics of chondroid cells from human adipose-derived Stem cells detected by atomic force microscopy

Chondroid cell from human adipose-derived stem cells (ADSCs) has emerged as an alternative treatment option for articular cartilage defects. Herein, we successfully compared ADSCs, normal chondrocytes, and chondroid cells. The comparative study of ADSCs and chondroid cells revealed type II collagen (COL II) and glycosaminoglycans expression of chondroid cells were similar to those in normal chondrocytes, and much higher than ADSCs. Using atomic force microscope (AFM) and laser confocal scanning microscopy (LCSM), we compared the differences in morphology, mechanical properties, and F-actin distribution between chondroid cells and normal chondrocytes. Our results showed no differences observed between these two types of cells regarding morphology, stiffness, and F-actin distribution. However, found that the adhesion force in chondroid cells was lower than that in normal chondrocytes. Taken together, our AFM and LCSM analyses suggest that the lower adhesion force in chondroid cells may contribute to the dedifferentiation of ADSC-derived chondroid cells. Future examination of surface adhesion force-related protein expression will likely provide new insight into the molecular mechanisms underlying the dedifferentiation of ADSC-derived chondroid cells.     

Neuron survival in vitro is more influenced by the developmental age of the cells than by glucose condition

The objective of this study was to determine whether the sensitivity to varying glucose conditions differs for the peripheral and central nervous system neurons at different developmental stages. Ventral horn neurons (VHN) and dorsal root ganglion neurons (DRG) from rats of different postnatal ages were exposed to glucose-free or glucose-rich culture conditions. Following 24 h at those conditions, the number of protein gene product 9.5 positive (PGP⁺) DRG neurons and choline acetyltransferase positive (ChAT⁺) VHN were counted and their neurite lengths and soma diameters were measured. For both DRG and VHN, the highest number of cells with and without neurite outgrowth was seen when cells from postnatal day 4 donors were cultured, while the lowest cell numbers were when neurons were from donors early after birth and grown under glucose-free conditions. The length of the neurites and the soma diameter for VHN were not affected by either glucose level or age. DRG neurons, however, exhibited the shortest neurites and smallest soma diameter when neurons were obtained and cultured early after birth. Our results indicate that survival of neurons in vitro is more influenced by the developmental stage than by glucose concentrations.     

A new RAPD marker for beet necrotic yellow vein virus resistance gene in Beta vulgaris

RAPD markers linked to beet necrotic yellow vein virus (BNYVV) resistance genes were identified in two Beta vulgaris accessions Holly-1-4 and WB42 using bulked segregant analysis. The polymorphism revealed by the RAPD markers in the F₂ generations of WB42 was higher than that of Holly-1-4. The segregation distortion at marker loci was slightly lower in the B. vulgaris × B. maritima cross than in the B. vulgaris × B. vulgaris cross. For Holly-1-4, a RAPD marker was identified in a long distance from the resistance gene of Rz ₁ . However, a RAPD marker tightly linked with Rz ₂ gene in repulsion phase was detected with an approximate distance of 0.036 rf. This marker was not generation specific and showed high repeatability. The distance between Rz ₁ and Rz ₂ genes was estimated as 0.464 rf. After the Rz ₂ Rz ₂ and Rz ₂ rz ₂ genotypes were identified using ELISA values and repulsion phase RAPD markers, comparison of their ELISA means revealed lack of the gene dosage effects. Nevertheless, under the field or severe infection conditions, the difference between ELISA mean values of the Rz ₂ Rz ₂ and Rz ₂ rz ₂ genotypes might be more than that observed in this study and the gene dosage effects of Rz ₂ allele might be important.     

Meta‐analysis Added Power to Identify Variants in FTO Associated With Type 2 Diabetes and Obesity in the Asian Population

Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10^?3; rs9939609, P = 9.8 × 10^?4; for obesity, rs8050136, P = 2.2 × 10^?7; rs9939609, P = 9.0 × 10^?9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.     

IndexToolkit: an open source toolbox to index protein databases for high-throughput proteomics

A software package, IndexToolkit, aimed at overcoming the disadvantage of FASTA-format databases for frequent searching, is developed to utilize an indexing strategy to substantially accelerate sequence queries. IndexToolkit includes user-friendly tools and an Application Programming Interface (API) to facilitate indexing, storage and retrieval of protein sequence databases. As open source, it provides a sequence-retrieval developing framework, which is easily extensible for high-speed-request proteomic applications, such as database searching or modification discovering. We applied IndexToolkit to database searching engine pFind to demonstrate its effect. Experimental studies show that IndexToolkit is able to support significantly faster searches of protein database. AVAILABILITY: The IndexToolkit is free to use under the open source GNU GPL license. The source code and the compiled binary can be freely accessed through the website http://pfind.jdl.ac.cn/IndexToolkit. In this website, the more detailed information including screenshots and documentations for users and developers is also available.