Systematic review of comparative transcriptomic studies of cellular resistance to genotoxic stress.

The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.

[Toothpastes of the «Mexidol dent¼ line - parapharmaceuticals with stable antioxidative activity]. / Zubnye pasty lineiki «MEXIDOL dent¼ ­ parafarmatsevticheskie preparaty s ustoichivoi antioksidantnoi aktivnost'yu.

THE AIM OF THE STUDY: Was to assess the stability of antioxidative activity of the active compound 2-ethyl-6-methylpiridine-3-ol succinate of toothpastes of the «Mexidol dent¼ line. MATERIALS AND METHODS: The study involved toothpastes of «MEXIDOL dent¼ line: MEXIDOL dent Aktiv MEXIDOL dent Complex, MEXIDOL dent Sensitive, MEXIDOL dent Fito, MEXIDOL dent Teens, MEXIDOL dent Professional White. Features of 2-ethyl-6-methylpiridine-3-ol succinate («MEXIDOL¼) determined the choice of potentiometric titration method for the assessment of the stability of antioxidative activity. RESULTS AND CONCLUSION: The study confirmed the stability of antioxidative activity of the active compound 2-ethyl-6-methylpiridine-3-ol succinate of toothpastes of the «Mexidol dent¼ line during shelf life.

Fatty acids composition and food consumption among reindeer herders and urban inhabitants of the European North of Russia.

INTRODUCTION: The goal of this study was to examine the fatty acid (FA) composition of the total plasma lipids of the native inhabitants of the Russian European North, taking into consideration the differences in lifestyles and nutritional habits as well as the interrelationship between the plasma FA profile and nutrition. METHODS: In total, 78 native residents of the Russian European North (61 men and 17 women) from two regions of Komi Republic of Northern Russia (Izhma settlement and city Syktyvkar), aged 25-45 years, were included in this study. The Izhma group consisted of reindeer herders (17 men and 17 women). The comparison group (44 men) consisted of citizens of Syktyvkar. Venous blood plasma after overnight fasting was used for analysis of glucose, cholesterol, triglycerides, vitamins and total FA composition. A modified questionnaire 'Seafood and the health of the people of the North' was used for the assessment of nutrition. RESULTS: The levels of total FAs in the blood plasma of Indigenous inhabitants of Russian European North were at the lower border of the reference range. In the Izhma group, levels of n-3 eicosapentaenoic acid (EPA) (1.3/0.9-1.8; p<0.001) and docosahexaenoic acid (DHA) (2.2/1.5-2.8; p=0.025), n-7 palmitoleic FA (2.3/1.9-2.5; p<0.001) were higher than in the Syktyvkar group. At the same time, levels of n-6 linoleic acid (32.1/29.2-35.5; p=0.003) were significantly lower in the male reindeer herders of Izhma. Comparison of the nutritional habits of both groups revealed larger consumption of fish, meat and reindeer fat (p<0.001), eggs (p=0.004), high-carbohydrate products (white bread (p=0.033) and macaroni (p<0.001)) by reindeer herders of Izhma. The participants in the urban group demonstrated higher consumption of fruits (p<0.001), butter (p=0.013), cultured milk foods (p=0.010) and vegetables (p=0.009). CONCLUSIONS: The results of the study showed more beneficial n-6/n-3 FA ratios in reindeer herders of Russian European North than in urban inhabitants. Higher plasma polyunsaturated n-3 FA (EPA, DHA) levels in reindeer herders who had more fish in their diet were demonstrated. In addition, inland reindeer herders showed higher palmitoleic acid levels and lower linoleic acid levels in blood total lipids than urban inhabitants. The nutritional features and environmental conditions were assumed to have the greatest effects on plasma FA profiles and lipid metabolism in the Indigenous inhabitants of Russian European North.

[Effects of acute normobaric hypoxia on free plasma amino acids metabolism in humans].

We demonstrated significant changes in levels of several plasma free amino acids--proline, hydroxyproline, glycine, and phenylalanine--in healthy volunteers in response to severe acute normobaric hypoxia (breathing nitrogen-oxygen mixture with 9% of O2). We assume that demonstrated an increase of free proline, hydroxyproline, and glycine in plasma in the 10th minute of hypoxia was caused by increased collagenolysis due to hypoxic activation of matrix metalloproteinases. Significantly increased levels of free phenylalanine in the 10th and 20th minutes of hypoxia were the consequences of autophagy activation. Our results suggest that acute severe normobaric hypoxia has specific effects on plasma free amino acids in healthy humans.