An integrated analysis of the association between Ts gene polymorphisms and clinical outcome in gastric and colorectal cancer patients treated with 5-FU-based regimens

Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.     

Reproductive biology of Oxygymnocypris stewartii in the Yarlung Zangbo River in Tibet, China

We determined the gonadal histology, reproductive characteristics and implications for management of Oxygymnocypris stewartii from individuals collected in the Yarlung Zangbo River. Based on the analyses of gonad development and the size distribution of oocytes, O. stewartii spawns just once each year. Peak spawning occurred between late March and early April, when water temperature exceeded 5°C. The standard lengths and the ages at 50 % maturity for males and females were 273 mm and 357 mm, and 5.1 year and 7.3 years, respectively. The mean fecundity of 34211 and mean relative fecundity of 25.4 eggs per gram of fish body weight suggest that O. stewartii might be especially vulnerable to exploitation.     

π–π Stacking mediated drug–drug interactions in human CYP2E1

Because of having many low molecular mass substrates, CYP2E1 is of particular interests to the pharmaceutical industry. Many evidences showed that this enzyme can adopt multiple substrates to significantly reduce the oxidation rate of the substrates. The detailed mechanism for this observation is still unclear. In the current study, we employed GPU‐accelerated molecular dynamics simulations to study the multiple‐binding mode of human CYP2E1, with an aim of offering a mechanistic explanation for the unexplained multiple‐substrate binding. Our results showed that Thr303 and Phe478 were key factors for the substrate recognition and multiple‐substrate binding. The former can form a significant hydrogen bond to recognize and position the substrate in the productive binding orientation in the active site. The latter acted as a mediator for the substrate communications via π–π stacking interactions. In the multiple‐binding mode, the aforementioned π–π stacking interactions formed by the aromatic rings of both substrates and Phe478 drove the first substrate far away from the catalytic center, orienting in an additional binding position and going against the substrate metabolism. All these findings could give atomic insights into the detailed mechanism for the multiple‐substrate binding in human CYP2E1, providing useful information for the drug metabolism mechanism and personalized use of clinical drugs. Proteins 2013; © 2012 Wiley Periodicals, Inc.     

Mesenchymal stem cells protect cigarette smoke‐damaged lung and pulmonary function partly via VEGF–VEGF receptors

Progressive pulmonary inflammation and emphysema have been implicated in the progression of chronic obstructive pulmonary disease (COPD), while current pharmacological treatments are not effective. Transplantation of bone marrow mesenchymal stem cells (MSCs) has been identified as one such possible strategy for treatment of lung diseases including acute lung injury (ALI) and pulmonary fibrosis. However, their role in COPD still requires further investigation. The aim of this study is to test the effect of administration of rat MSCs (rMSCs) on emphysema and pulmonary function. To accomplish this study, the rats were exposed to cigarette smoke (CS) for 11 weeks, followed by administration of rMSCs into the lungs. Here we show that rMSCs infusion mediates a down‐regulation of pro‐inflammatory mediators (TNF‐α, IL‐1β, MCP‐1, and IL‐6) and proteases (MMP9 and MMP12) in lung, an up‐regulation of vascular endothelial growth factor (VEGF), VEGF receptor 2, and transforming growth factor (TGFβ‐1), while reducing pulmonary cell apoptosis. More importantly, rMSCs administration improves emphysema and destructive pulmonary function induced by CS exposure. In vitro co‐culture system study of human umbilical endothelial vein cells (EA.hy926) and human MSCs (hMSCs) provides the evidence that hMSCs mediates an anti‐apoptosis effect, which partly depends on an up‐regulation of VEGF. These findings suggest that MSCs have a therapeutic potential in emphysematous rats by suppressing the inflammatory response, excessive protease expression, and cell apoptosis, as well as up‐regulating VEGF, VEGF receptor 2, and TGFβ‐1. J. Cell. Biochem. 114: 323–335, 2013. © 2012 Wiley Periodicals, Inc.     

Redox potential control and applications in microaerobic and anaerobic fermentations

Many fermentation products are produced under microaerobic or anaerobic conditions, in which oxygen is undetectable by dissolved oxygen probe, presenting a challenge for process monitoring and control. Extracellular redox potentials that can be detected conveniently affect intracellular redox homeostasis and metabolism, and consequently control profiles of fermentation products, which provide an alternative for monitoring and control of these fermentation processes. This article reviews updated progress in the impact of redox potentials on gene expression, protein biosynthesis and metabolism as well as redox potential control strategies for more efficient production of fermentation products, taking ethanol fermentation by the yeast Saccharomyces under microaerobic conditions and butanol production by the bacterium Clostridium under anaerobic conditions as examples.     

Effect of aboveground intervention on fine root mass, production, and turnover rate in a Chinese cork oak (Quercus variabilis Blume) forest

Aims

Fine root is an important part of the forest carbon cycle. The growth of fine roots is usually affected by forest intervention. This study aims to investigate the fine root mass, production, and turnover in the disturbed forest.

Methods

The seasonal and vertical distributions of fine root (diameter ≤2 mm) were measured in a Chinese cork oak (Quercus variabilis Blume) forest. The biomass and necromass of roots with diameters ≤1 mm and 1-2 mm in 0-40 cm soil profiles were sampled by using a sequential soil coring method in the stands after clear cutting for 3 years, with the stands of the remaining intact trees as the control.

Results

The fine root biomass (FRB) and fine root necromass (FRN) varied during the growing season and reached their peak in August. Lower FRB and higher FRN were found in the clear cutting stands. The ratio between FRN and FRB increased after forest clear cutting compared with the control and was the highest in June. The root mass with diameter ≤1 mm was affected proportionately more than that of diameter 1-2 mm root. Clear cutting reduced FRB and increased FRN of roots both ≤1 mm and 1-2 mm in diameter along the soil depths. Compared with the control, the annual fine root production and the average turnover rate decreased by 30.7 % and 20.7 %, respectively, after clear cutting for 3 years. The decline of canopy cover contributed to the dramatic fluctuation of soil temperature and moisture from April to October. With redundancy discriminate analysis (RDA) analysis, the first axis was explained by soil temperature (positive) and moisture (negative) in the control stands. Aboveground stand structure, including canopy cover, sprout height, and basal area, influenced FRB and FRN primarily after forest clear cutting.

Conclusions

This study suggested that the reduction of fine root biomass, production, and turnover rate can be attributed to the complex changes that occur after forest intervention, including canopy damage, increased soil temperature, and degressive soil moisture.