Vitamin D is a unique compound that can enter the human body not only with food, but also be synthesized in the skin under the influence of ultraviolet radiation. Individual differences in the need for this vitamin may be associated with the carriage of polymorphic variants of genes that implement its biological effects, which include VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G. At risk for vitamin D deficiency are workers in the coal mining industry, whose working conditions combine limited insolation and a pronounced deficiency of vitamins in the diet. The purpose of the study was to assess vitamin D plasma level in coal mining workers depending on the carriage of polymorphic variants of the VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G genes and professional working conditions. Material and methods. The study included 154 coal mining workers. The main group consisted of 100 workers associated with the underground nature of work, the comparison group - 54 ground workers of the enterprise. In all individuals, the level of 25-hydroxyvitamin D in blood plasma was determined by enzyme-linked immunosorbent assay and genotyping was performed for three polymorphic loci: VDR rs1544410, rs731236, GC rs2282679 by real-time PCR. Results. A statistically significant decrease in the concentration of plasma vitamin D in the underground workers was revealed, compared with the level of this vitamin in ground workers of the enterprise (p=0.037). Underground workers - carriers of the CT genotype of the VDR rs1544410 gene, AG of the VDR rs731236 gene and TT of the GC rs2282679 gene had a lower 25(OH)D level in blood plasma compared to owners of similar genotype variants in the comparison group (p<0.05). Among ground workers, carriers of the TT genotype of the GC rs2282679 gene had a significantly higher vitamin D plasma level compared to carriers of the TG and GG genotypes (p=0.02). An association of the GC gene with vitamin D level in blood plasma was revealed according to a dominant model of inheritance (OR=0.47, 95% CI 0.23-0.97; p=0.037, for owners of the TT genotype, compared with carriers of the TG+GG genotypes). Conclusion. The development of personalized diets based on individual genetic status may be of great importance for the prevention of diseases associated with vitamin D deficiency in individuals at risk.
Breast cancer is one of the leading causes of mortality among women. The most frequently encountered tumors are luminal tumors. Associations of polymorphisms in the hOGG1 (rs1052133), APEX1 (rs1130409), XPD (rs13181), SOD2 (rs4880), and CAT (rs1001179) genes were studied in 313 nonsmoking postmenopausal patients with luminal B subtype breast cancer. The control group consisted of 233 healthy nonsmoking postmenopausal women. Statistically significant associations of the XPD and APEX1 gene polymorphisms with the risk of developing luminal B Her2- negative subtype of breast cancer were observed in a log-additive inheritance model, while the CAT gene polymorphism showed an association in a dominant inheritance model (OR = 1.41; CI 95 %: 1.08–1.85; Padj.= 0.011; OR = 1.39; CI 95 %: 1.07–1.81; Padj = 0.013 и OR = 1.70; CI 95 %: 1.19–2.43; Padj = 0.004, respectively). In the group of elderly women (aged 60–74 years), an association of the CAT gene polymorphism with the risk of developing luminal B subtype of breast cancer was found in a log-additive inheritance model (OR = 1.87; 95 % CI: 1.22–2.85; Padj = 0.0024). Using MDR analysis, the most optimal statistically significant 3-locus model of gene-gene interactions in the development of luminal B Her2-negative subtype breast cancer was found. MDR analysis also showed a close interaction and mutual enhancement of effects between the APEX1 and SOD2 loci and the independence of the effects of these loci from the CAT locus in the formation of luminal B subtype breast cancer.
An analysis was made of the relative length of telomeres and rs2736100 polymorphic variants of the TERT gene in 123 patients diagnosed with lung cancer and 120 healthy individuals. The telomeres of cancer patients turned out to be statistically significantly longer (p<0,001) compared to healthy ones. Depending on the carriage of various variants of the TERT genotypes, there were no significant differences in telomere length in both groups.
Breast cancer (BC), with nearly 1.7 million incidence and 522,000 deaths (according to GLOBOCAN statistics), is the most frequently occurring cancer in women. The etiology of BC is multifactorial and has not been fully elucidated. However, genetic factors are known to increase or decrease susceptibility to BC, suggesting that genetic polymorphisms play an important role in the oncopathology. Accordingly to these facts, the aim of our study was the analysis of polymorphic variants of DNA repair genes ADPRT 2285 A>G rs113641 in BC patients and conditionally healthy women of Kemerovo region.
Non-communicable diseases often occur due to an unbalanced diet. Cardiovascular diseases that develop due to oxidative stress are in the first place in mortality. To reduce the risk of diseases of the cardiovascular system, geroprotectors are used, in large quantities contained in vegetables. Natural substances of this type include ascorbic acid and chlorophyll, which have antioxidant activity and are part of broccoli cabbage. These substances contribute to the prevention of cardiovascular diseases. Diseases of the gastrointestinal tract also occur due to malnutrition (leads to a decrease in the amount of beneficial intestinal microflora). Eating cottage cheese and products based on it helps to replenish the necessary amount of natural intestinal microflora, due to fermented milk bacteria. The purpose of the work is to develop a functional curd product with the addition of mashed broccoli. During the study, it was found that the titrated acidity of the curd mass with broccoli puree was 113.0 ° T, the mass fraction of moisture, sucrose, protein and fat – 40,5 %, 10,8 %, 15,7 %, 4,2 %, accordingly, the energy value of 100 g of the product is 110 kcal. The number of lactic acid bacteria is 13×106 CFU/g. Conditionally pathogenic microorganisms were not detected during the study. The antioxidant activity of the curd mass with broccoli was 55.02%, which is 30.55% more than that of the curd mass without additives. The amount of chlorophyll was 24.36 mg/100g of the product. Due to the introduction of broccoli into the curd mass, the content of B1 increased by 1.45 mg/100g of the product; B3 – 1.69 mg/100g of the product; B6 – 0.01 mg/100g of the product; C – 102.8 mg/100g of the product. Thus, the developed curd mass with broccoli is a functional food product for the prevention of diseases of the cardiovascular system and gastrointestinal tract.
Green tea is one of the most popular drinks consumed in the world. Important components contained in green tea and having antioxidant and anticarcinogenic properties are catechins - organic substances belonging to the class of polyphenolic compounds. Green tea contains 4 main catechins: (-)-epicatechin, (-)-epicatechin-3-gallate, (-)-epigallocatechin and (-)-epigallocatechin-3-gallate. This review summarizes the results of key studies, predominantly performed over the last 5 years, which provide evidence that catechins in green tea protect against ultraviolet radiation, can improve the quality of life of patients suffering from cancer, cardiovascular, neurodegenerative, viral, infectious diseases, obesity and a number of other pathologies, as well as serve as a measure for the prevention of these diseases in healthy individuals. The most potent catechin found in green tea has been shown to be (-)-epigallocatechin-3-gallate. The anticarcinogenic effects of (-)-epigallocatechin-3-gallate in the case of prostate cancer, breast cancer, colorectal cancer are presented. The powerful antioxidant activity of catechins can form the basis for the prevention of the development of infectious and viral diseases, as well as improve the quality of life of patients with metabolic syndrome and obesity. Thus, green tea is not only a tonic drink, but also an important tool for the prevention and treatment of human diseases, in the pathogenesis of which free radical oxidation and oxidative stress play an important role. The areas of practical application of green tea catechins can be the treatment of malignant tumors (during a course of chemotherapy or radiation therapy), the treatment of viral, infectious and cardiovascular diseases, skin protection from ultraviolet rays, etc.
At present time it is noticed significant interest for ability of biologically active compounds usage not only for prevention but also for therapy of human diseases. Traditionally medical plants with high pharmacological potential are rich source for them. Therapeutical features of plants were demonstrated on example of many widespread human diseases. In this systematic review perspectives of plant extracts application in lung cancer therapy has been discussed. It was carried out research of scientific publications using Medline, Scopus, WoS, Pubmed databases. Their text was published in open access in English. As a result of analysis it was made a conclusion about significant therapeutical potential of plant extracts and perspectives of development of new strategies of lung cancer treatment, that are included biologically active compounds with classical approaches (chemoterapeutical agents, target substances and radiation).
Lung cancer (LC) is leading oncological pathology, posing a serious threat for patient’s lives. Accordingly to World Health Organization (WHO) 2,1 million of new cases and 1,8 of deaths are annually registered. It was accumulated a lot of information about significant influence of smoking on increased risk of LC development. 80-90% of patients with LC are namely smokers. However at present time it was registered increased level of mortality from this pathology among non-smoking patients [1]. LC formation in non-smoking individuals can occur due to environmental pollution by industrial and household cancerogens and also because of molecular and genetical and cytogenetical dissimilarities. Since LC development can be associated with anomalous immunological response, immune genes can be considered as potential biological markers [2]. Objective: To assess the influence of polymorphic variants of innate immunity genes on LC development in non-smoking patients.
Dioscorea Caucasica is a source of various biologically active substances (BAS), e.g. saponins and polyphenols, which are known for their anti-atherosclerotic action. However, this species is in the Red List of many Russian regions. Biotechnological methods of production of callus, suspension, and root cultures in vitro can solve this problem. The research objective was to select the optimal BAS extraction parameters. The study featured in vitro cell cultures, grown according to standard methods, and extracts, obtained from these cultures using various organic solvents and extraction parameters, i.e. temperature, the ratio of raw material vs. extractant, time, etc. The best yield of the extract from callus cultures was observed when methanol was applied in a ratio of 1:10 at 40°C for 60 min. As for suspension cultures, the greatest yield was provided by isopropanol in a ratio of 1:10 at 40°C for 30 min. In case of root cultures, the most effective combination was that of isopropanol in a ratio of 1:10 at 40°C for 60 min. The root culture proved the source of the highest BAS content, namely caffeic acid, rutin, mangiferin, quercetin, and apigenin. The content of rutin was 13 and 22 times higher than that of callus and suspension cultures. TLC, HPLC, and NMR procedures demonstrated that the isopropanol extract contained such saponins as glucopyranoside, rhamnopyranoside, deltoside, protodioscin, spirosthenol A, and spirosthenol B. These substances are known for their antiatherosclerotic properties. Therefore, in v itro cell cultures of Dioscorea Caucasica can be used as raw materials for various pharmaceutical purposes, as well as in functional foods.
Воздействие комплекса факторов производственной среды предприятий угольного цикла, может привести к возникновению различных легочных заболеваний. Подтвержденным биомаркером генотоксического воздействия, отражающим индивидуальную чувствительность к воздействию факторов окружающей среды, является частота хромосомных аберраций в лимфоцитах периферической крови человека. Цель: изучение хромосомной нестабильности в клетках периферической крови у рабочих угольных шахт Кузбасса и у больных раком легкого, имеющих стаж работы на угольных шахтах Кузбасса. Материалом для исследования послужила периферическая кровь. Культивирование лимфоцитов крови для получения препаратов хромосом осуществляли стандартным полумикрометодом. Стaтистическaя обрaботкa проводилaсь с использовaнием методов непараметрической статистики, реализованных в программе «Statistica 10.0» (StatSoft, Inc., USA). Выявлено статистически значимое повышение частоты аберрантных метафаз у рабочих угольных шахт Кузбасса и у больных раком легкого, имеющих стаж работы на угольных шахтах Кузбасса, по сравнению со здоровыми донорами из группы сравнения. Mining has a direct impact on the environment and on the health of miners and is considered one of the most hazardous occupations worldwide. The aim of this study was the analysis of chromosomal aberrations (CAs) in lung cancer patients and healthy donors resident in the same territory. Statistical analysis were performed using nonparametric statistics (Mann-Whitney U Test for paired comparison of quantitative characteristics), logistic regression. It was determined that the CAs frequency (both chromatid- and chromosome-type aberrations) was significantly increased in lung cancer patients compared to control group.
Цель: изучение ассоциаций полиморфизма генов FTO, FABP2, PPARG и ожирения у жителей Кузбасса. Методы. Выборка для исследования составила 395 мужчин, жителей Кузбасса. Средний возраст испытуемых составил 59±7,7 года. Согласно анкетным данным, все обследованные мужчины отнесли себя к русской национальности. Частота ожирения в данной выборке (индекс массы тела>30) составила 46,3%. Генотипирование полиморфных вариантов FTO (rs9939609), FABP2 (rs1799883) и PPARG (rs1801282) проводилось с использованием TaqMan PCR. Далее проводилась проверка ассоциации данных полиморфных вариантов с ожирением в различных моделях наследования. Результаты. Были выявлены ассоциации вариантов гена FTO rs9939609 с ожирением в кодоминантной (для генотипа T/A OR = 2,05; СI: 1,26-3,33; р = 0,004; для генотипа A/A (OR = 2,27; CI: 1,28-4,04; р= 0,004) и доминантной модели наследования (OR = 2,12; CI: 1,34-3,34 р= 0,001). Другие гены не показали значимой связи с ожирением в нашей выборке. Заключение. Вариант rs9939609 гена FTO ассоциирован с повышенным риском развития ожирения у мужчин, проживающих в Кузбассе. Purpose: To investigate the associations of FTO, FABP2, PPARG gene polymorphism and body mass index in Kuzbass residents. Methods. The sample for the study was 395 men, residents of Kuzbass. The average age of the subjects was 59±7.7 years. According to the questionnaire data, all the examined men referred themselves to the Russian nationality. The frequency of obesity in this sample (body mass index>30) was 46.3%. Genotyping of 3 polymorphic variants: FTO (rs9939609), FABP2 (rs1799883), and PPARG (rs1801282) were performed using TaqMan PCR. The association of these polymorphic variants with obesity in various inheritance models was then tested. Results. The associations of FTO rs9939609 gene variants with obesity in the codominant (for genotype T/A OR = 2.05; CI: 1.26-3.33; p = 0.004; for genotype A/A (OR = 2.27; CI: 1.28-4.04; p = 0.004) and dominant inheritance models (OR = 2.12; CI: 1.34-3.34 p = 0.001) were detected. Other genes showed no significant association with obesity in our sample. Conclusion. The rs9939609 variant of the FTO gene is associated with an increased risk of obesity in Kuzbass residents.
DNA-methyltransferases catalyze DNA methylation in the CpG sites, which play an important role in the maintenance of genome stability. The association between DNA methylation and genotoxic stress resulting in the action of various clastogens has been shown. Genotoxic stress is one of the triggers of endothelial dysfunction. In this study, the transcription of DNMT1, DNMT3A and DNMT3B genes in coronary (HCAEC) and internal thoracic (HITAEC) artery endothelial cells exposed to alkylating mutagen mitomycin C was studied using quantitative polymerase chain reaction. In HCAEC exposed to mitomycin C, DNMT1 transcription is 1.7-fold higher compared to the unexposed control. After elimination of the mutagen from the cultures followed by 24-hours of cultivation, a 2-fold increase of transcription of DNMT3B in HCAEC exposed to mitomycin C compared to the control was observed. At the same time, no changes in transcription of the studied DNA-methyltransferases were found in HITAEC exposed to the mutagen. Thus, increased transcription of DNA-methyltransferase may be a possible molecular mechanism underlying endothelial dysfunction in response to mutagenic load in an in vitro experiment.
Lung cancer is the most commonly occurring cancer in men worldwide. To search for new biological markers of this pathology, the transcriptome of the blood mononuclear cells from patients and healthy donors (residents of Kemerovo oblast, Russia) was studied using SurePrint G3 Human Gene Expression microarray technology. A total of 288 differentially expressed genes were identified, including 108 up-regulated genes and 180 down-regulated genes. Functional enrichment analysis using the WebGestalt resource and different databases (Gene Ontology, KEGG, and Reactome) indicated changes in the expression profiles of genes involved in the processes of immune response, protein synthesis, cell cycle control, and apoptosis. Analysis of protein–protein interactions using the STRING algorithm made it possible to identify functional clusters of gene products with different expression levels.
Prolongation of life expectancy and improvement of phenotypes directly related to the aging process have been the objects of many studies. Some of the known methods of increasing life expectancy, including dietary restrictions and genetic manipulation, are difficult to apply to all people, and their side effects are difficult to predict. It is for this reason that it becomes important to find those biologically active compounds that can act as anti-aging agents or can induce prolongation of life due to various metabolic processes inside the cell. The medicinal plant SFO thyme (Thymus vulgaris L.) is a source of many active compounds that can affect life expectancy. The present study was conducted to evaluate the effect of biologically active compounds of the extract of the callus culture of Thymus vulgaris L., dried by spray drying at different temperature conditions (60 ℃, 90 ℃, 120 ℃), on the growth of the experimental model Saccharomyces cerevisiae Y-564. Anti-aging effect of dry extract of callus culture Thymus vulgaris L. with concentrations of 0.25 mg/ml, 0.50 mg/ml and 1.00 mg/ml on a model yeast organism, the yeast cells were evaluated by increasing the biomass of yeast cells. The results of the studies showed that the best variant of the effect of the growth properties of the biomass of the yeast suspension S. cerevisiae Y-564 showed an extract of the callus culture Thymus vulgaris L., dried at a temperature of 90 ℃, with a concentration of 0.50 mg / ml. It was under such conditions that a stimulating increase in the biomass of the test culture was observed. These results of this study provide new insights into the mechanisms by which biologically active compounds extracted from the callus culture of Thymus vulgaris L. can slow down the aging process.
Обследованы 559 шахтеров, работающих на угольных шахтах Кемеровской области, в том числе 236 человек с диагностированным раком легкого (59±7,8 лет) и 323 человека, проживающие в той же местности и не имеющие признаков онкологических заболеваний (54±8,4 лет). Проведен сравнительный анализ полиморфных вариантов гена MMP1 -1607insG (rs1799750). Анализ выявил значимую ассоциацию между риском рака легкого у шахтеров и генотипом 2G/2G гена MMP1 (OR = 1,55, CI: 1,08-2,21, p = 0,02, аллелем 2G (OR= 1,32 95% CI: 1,04-1,67, p=0,02). Показатели риска были более выражены в подгруппе курящих (для генотипа 2G/2G OR= 2,08 95% CI: 2,08 1,20-3,59, p=0,008; для аллеля 2G OR= 1,63 95%CI: 1,16-2,31, p=0,005). The study involved 559 miners living in the Kemerovo region of Russia were examined, including 236 patients with lung cancer and 323 without signs of oncological diseases. A comparative analysis of polymorphic variants of the MMP1 -1607insG (rs1799750) gene was carried out in miners with lung cancer and individuals without cancer living in the same area. Analysis of single-locus effects showed a significant relationship between the risk of lung cancer and the 2G/2G genotype of the MMP1 gene in the general group (OR = 1.55, CI: 1.08-2.21, p = 0.02) and the smoking group (OR= 2.08 95% CI: 2.08 1.20- 3.59, p=0.008). The 2G allele also showed a significant association with the risk of developing PD in miners in the general group (OR= 1.32 95% CI: 1.04-1.67, p=0.02) and the smoking group (OR= 1.63 95% CI: 1.16-2.31, p =0.005).
The study involved 522 women of Russian nationality living in Kemerovo oblast of Russia, including 273 patients with lung cancer and 249 women of a similar age with no signs of cancer. Comparative analysis of polymorphic variants of DNA repair genes APEX1 444T>G (rs1130409), XRCC1 1839G>A (rs25489), hOGG1 977C>G (rs1052133), XPD 2251Т>G (rs13181), XPG 3310G>C (rs17655), and XPC 2815A>C (rs2228001) in patients with lung cancer and individuals without cancer living in the same area was performed. Analysis of single-locus effects showed significant associations between the risk of lung cancer and variants of the XPC 2815A>C gene (rs2228001) (OR = 0.56, CI: 0.39–0.81, p = 0.0018) in the general group, the APEX1 444T>G gene (rs1130409) (OR = 0.15, CI: 0.03–0.67, p = 0.0027) in the group of smokers, and genes XPC 2815A>C (rs2228001) (OR = 0.36, CI: 0.18–0.69, p = 0.0051) and hOGG1 977C>G (rs1052133) (OR = 0.57, CI: 0.38–0.85, p = 0.0055) in the group of nonsmokers. MDR analysis of gene-gene interactions showed that genes XPD 2251Т>G and XPC 2815A>C, APEX1 444T>G, and XPD 2251Т>G closely interact and mutually increase the risk of lung cancer in women of Western Siberia.
Carcinogenesis is associated with a stepwise accumulation of genetic changes induced by the action of various genotoxic environmental factors (heavy metals, polycyclic aromatic hydrocarbons, radioactive substances, and others). Comorbid pathology can make a significant contribution to the accumulation of genome damage, influence the effectiveness of treatment, and determine the overall prognosis of survival. 50 men with lung cancer were examined. The control group included 84 men without oncopath-ology of close age, living in the same area. A micronucleus assay was performed on blood lymphocytes. The analysis of binuclear lymphocytes with micronuclei, protrusions, nucleoplasmic bridges revealed a statistically significant difference between the patient groups and the control. An increase in the frequency of occurrence of these markers of cytogenetic disorders in patients with lung cancer was noted. A higher replication index was recorded in the control group. In patients with lung cancer and concomitant ischemic heart disease, differences in the frequency of mononuclear lymphocytes with micronuclei and the frequency of apoptosis were recorded as compared with patients without cardiovascular diseases.
Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.