代谢组学：开放获取

The treatment of breast cancer has been undergoing an incredible sequence of changes. The role of individual treatment of women with breast cancer is not clearly defined. Since last century the drug 5-fluorouracil with another anticancer agents and prodrugs from group of fluoropyrimidines are widely used. Thymidine phosphorylase is the enzyme which can also catalyze the interconversion of uracil as well as several fluoropyrimidines. Thymidine Phosphorylase (TP) and Thymidine Kinase (TK) also play an important role in thymidine homeostasis and thus in DNA synthesis. Thymidine kinase is used as cells proliferation marker. Thymidine phosphorylase is similar to the platelet-derived endothelial cells growth factor. High expression of the enzyme is related to malignant angiogenesis and invasion. That is why we investigated the activity of TK and TP both in healthy women and patients with breast cancer (BC) of the I–IV stages and of the same age. Analysis of biochemical and morphological data of these patients revealed that the patients are initially divided according to the activity of blood plasma TP also had different morphological structure of the tumor. In the 1-st group the initial activity of TP was sharply reduced and in the 2nd group TP activity ranged normally. During the treatment of women from the 1st group the activity of TP was not changed, but the activity of TK was increased 3 times. In patients from the 2nd group the activity of TP was authentically increased, but TK activity was reduced. The follow-up analysis showed that four-year lethality in the 1-st group constituted 25%, and there was no lethality in the the 2nd group. Therefore the studied enzymes activity may be used as the informative test for monitoring of patients with breast cancer and optimization of drug treatment.

Purpose: Smoke from cigarette smoking (CS) has been proposed to be a major environmental risk factor for a variety of human diseases and was implicated also in cataract, an eye lens pacification, which is a major cause of blindness. We have undertaken a study to investigate the effect of smoke on the physiological integrity and metabolism of organ cultured lenses. Lenses in organ culture are metabolically active and have functional defense systems, thus they provide an appropriate model for studying the effects of smoke. Also the possible protective action of N-acetylL-cysteine (NAC) which is a precursor of glutathione and the iron chelators Deferoxamine (DFO), was estimated as potential protective agents against cataract.

Methods: Bovine lenses were incubated in organ culture conditions at 35°Cfor 6 days. Treated lenses were 4 day in the culturally environment daily sated with a cigarette smoke under various doses of pressure-250,500 psi. Two of the experimental groups were treated with NAC (1 mM) and DFO (2.5 µg/ml) as antioxidants. An automated scanning laser system was used for daily testing of both treated and control lenses. At the end of the culture period, lenses were analyzed by inverted microscopy. We have used preparations of the forward monolayer epithelium bovine lenses from all experiments. For this purpose the capsule opened and crystalline lens fibers were cleaned. On the object-plate them there was only a capsule and a cellular monolayer epithelium. Changes of morphology of cells and the contents of the nucleic acids was estimated using the Einarson - DNA-RNA staining method. Reactive Oxygen Species (ROS) were estimated with 5- (and 6-) chloromethyl-2’,7’-dichloro-dihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA, C6827) to measure the level of cellular oxidation in the cells of lens epithelium. The levels of ROS were measured by monitoring the fluorescent intensity relative to that of control cultures under fluorescent microscopy. Nucleic acids were stained with Propidium Iodide.

Results: Exposure of cigarette smoke in cultured medium under negative pressure, optical quality of lenses and the structural changes were demonstrated by decreased light transmission, increase in focal length variability and a decrease in morphological integrity such as hyperplasia and hypertrophy of epithelial cells. The group exposed to NAC and to DFO, demonstrated reduced optical changes representing smaller lens injury. The lenses show almost no volume changes. However, the baseline fluorescence of controls varied between experiments. A dose-dependent increase in ROS generation in cultures was also evident.

Conclusions: We have shown that increasing the amount CS exposure, for a relatively short time, causes a sharp increase in the damage to the lens. Smoking is an independent risk factor that has dose-response effects. It causes morphological and functional changes to the lens. Based on the independent effects of NAC and DFO, we propose to possibly use them as means of prevention and/or treatment of cataract in heavily smoking people.

The purpose of this study was to determine the relationship of osteocalcin with insulin resistance, insulin-like growth factor-1 (IGF-1) and inflammatory markers in women with RA.

The study population comprised of 35 postmenopausal women with RA. The significant negative correlations were noted between the osteocalcin and resistin levels (P <0.05), glucose and resistin levels (P ≤ 0.01), glucose and interleukin-6 levels (P ≤ 0.01), interleukin-6 and insulin-like growth factor binding protein-3 (IGFBP-3) levels (P < 0.05). The positive correlations were found between insulin level and disease duration (P < 0.05), index of insulin resistance (HOMA-IR) level and disease duration (P < 0.05), IGF-1 and IGFBP-3 levels (P ≤ 0.01), the IGF-1/IGFBP-3 ratio and erythrocyte sedimentation rate (P ≤ 0.01), and the IGF-1/IGFBP-3 ratio and C-reactive protein levels (P < 0.05).

The present study suggests that inflammatory factors may modify in distinct ways the relationship between osteocalcin and carbohydrate metabolism in patients with RA. However, limitations of this study are: lack of control group, small sample size and that we did not measure uncarboxylated OC.

Personalized cancer care strategies involving sequencing requires accuracy. We aimed to develop a novel
approach to solve the longest common subsequence problem, which is a common computer science problem in the field of bioinformatics to facilitate the next generation sequencing of cancer biomarkers. We are using particle swarm optimization heuristic technique, which uses a novel “Occurrence Listing” (OL) technique as the evaluation function. This aims to keep lists of the sequence elements and offers criteria to evaluate randomly generated population of sequences.