Aim. To study the activity of antitumor immunity effectors and to analyze possible mechanisms of peritoneal Mph M1/M2 repolarization of Balb/c mice under the influence of lectin from B. subtilis IMV B-7724 in the dynamics of the model tumor growth. Materials and Methods. Studies were performed on Balb/c mice; Ehrlich adenocarcinoma (АСЕ) was used as an experimental tumor. Lectin from B. subtilis IMV B-7724 was administered to ACE-bearing mice at a dose of 1 mg/kg of body weight, 10 times. Immunological testing was performed on days 21 and 28 after tumor grafting. The functional activity of peritoneal macrophages (Mph), natural killer (NK) cells, cytotoxic lymphocytes (CTL), and cytokine levels (IFN-γ, IL-4) were studied by the standard methods. mRNA expression levels of transcription factors STAT-1, STAT-6, IRF5, and IRF4 in Mph were evaluated. Results. The administration of lectin from B. subtilis IMV B-7724 to mice with solid ACE led to the preservation of the initial functional state of peritoneal Mph M1 during the experiment. The bacterial lectin ensured the preservation of the cytotoxic activity of CD8+ T-lymphocytes and a significant (p < 0.05) increase in the NK activity (by 2.7 times compared to the intact animals and by 12.9 times compared to the untreated mice). A strong positive correlation was noted between the levels of the functional activity of Mph and CD8+ T-lymphocytes of animals with tumors and the indices of the antitumor effectiveness of bacterial lectin. The indirect polarization of Mph was evidenced by a strong positive correlation between the level of the NO/Arg ratio (which characterizes the direction of Mph polarization) and the cytotoxic activity of CD8+ T-lymphocytes, NK cells, and the expression of STAT1/STAT6 (the 21st day) and IRF5/IRF4 (the 28th day). Conclusion. In ACE-bearing mice, repolarization of the peritoneal Mph toward M1 can occur not only due to the direct action of bacterial lectin on the cellular receptors but also with the involvement of other effectors of antitumor immunity (NK cells, T-lymphocytes). The transcription factors of the STAT and IRF signaling pathways are involved in the polarization process.
BACKGROUND:Analysis of immunoglobulin heavy chain gene (IGHV) rearrangements expressed in chronic lymphocytic leukemia (CLL) cells has provided insights into the B-cell receptor (BCR) repertoire in CLL. In more than 40% of CLL patients, (quasi)identical or stereotyped BCR is expressed. The recent data point at the non-stochastic expression of immunoglobulin light lambda (IGLV) or kappa (IGKV) chains as well. Several pairs of IGHV and IGK/LV have been described for some major stereotyped subsets, but most subsets have not been characterized. AIM:To study the IGK/LV gene expression in stereotyped CLL cases. MATERIALS AND METHODS:Analysis was performed in a group of 105 CLL patients with stereotyped BCR. The cases with stereotyped BCRs were identified according to Agathangelidis et al. (2021). The IGHV and IGK/LV gene expressions were studied by a polymerase chain reaction followed by direct sequencing. RESULTS:The expression of the IGK/LV genes in the most presented major stereotyped subsets (#1, #2, #3C3, #4, #6, #28а) was in agreement with the data reported by other authors. For the cases of subsets #5b, #9D1, #9D4, #16, #50, #59, and #77, differences were found. The new data on the IGK/LV gene expression in 55 minor clusters were presented. A number of patterns of the IGK/LV gene expression depending on the phylogenetic clan and mutational status of the IGHV genes have been described. CONCLUSION:The non-stochastic distribution of the IGKV/LV gene expression in the individual stereotyped subsets was confirmed. Taking into account the complementary role of the light chains in antigen recognition by the clonotypic BCRs, it was suggested that the subsets with the heterogeneous IGK/LV expression might be reclassified and divided into separate subgroups based on the IGHV and IGK/LV association.
Вступ. Збереження життя та здоров’я військовослужбовців в умовах радіаційних і ядерних загроз на період воєнного стану є одним з актуальних завдань сьогодення. Управління в умовах виникнення таких загроз має певні особливості, тобто має характерні риси, що відрізняють його від управління у звичайних повсякденних умовах. Мінімізувати наслідки та певною мірою попередити катастрофічні явища можна лише на підставі наукового прогнозування, яке базується на наукових дослідженнях в галузі медичній, державного управління, національної безпеки оскільки згадані вище події можуть виникати з різних причин та бути зумовленими різноманітними факторами, їх різними комбінаціями та взаємодією. Сьогодні в Україні не існує відповідної нормативно-правової бази, що регулювала б сценарії радіаційно-ядерних загроз в умовах війни та стосунки між органами військового управління з державними органами самоврядування. Мета. Проаналізувати чинну нормативно-правову базу в Україні щодо протирадіаційного захисту та радіаційної безпеки військовослужбовців. Матеріали та методи. Бібліографічний метод з можливістю так званого «згортання інформації»: на підставі бібліографічного вивчення інформації, яка існує у вигляді документів у відкритому доступі, аналітична обробка. створення нової, вторинної інформації. Системний підхід – один з спеціальних способів наукового дослідження, за яким досліджуваний об'єкт розчленовують на елементи, що їх розглядають в єдності, тобто як систему. Результати. В статті розглянуто питання необхідності розробки ключових документів, що підтримують готовність до реагування на можливі сценарії ядерних та радіаційних загроз у період воєнного стану. Крім того, необхідно відзначити, що принципи організації державного управління у звичайних умовах також відрізняються від аналогічних принципів в умовах радіаційно-ядерних подій у період воєнного часу. Це пов’язано з особливостями, до яких слід віднести слабку передбачуваність дійсного масштабу та часу їх виникнення; складність та багатоваріантність взаємозв’язків між процесами; часткову передбачуваність сценаріїв подальшого розвитку; надзвичайно високий рівень невизначеності. Висновки. Доведено необхідність розробки нормативних документів щодо реагування та планування безперервної діяльності з реагування на потенційні ядерні та радіаційні загрози у період воєнного стану, включаючи взаємозв’язки на всіх рівнях управлінської вертикалі та способи комунікації в разі реалізації загрози.
Research activities and scientific advance achieved in 2023 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine» (NRCRM) concerning medical problems of the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaboration with the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annual report. The report presents the results of fundamental and applied research works of the study of radiation effects and health effects of the Chornobyl accident. The institution has been reorganized and since December 2023 has been called the State Institution «National Research Center for Radiation Medicine, Hematology and Oncology» (NRCRM). The report also shows the results of scientificorganizational and health care work, staff training. The Scientific Council meeting of NAMS approved the NRCRM Annual Report.
Summary. CD38 antigen is a negative prognostic marker of chronic lymphocytic leukemia (CLL). The question of what cut-off level of CD38 antigen expression should be considered as prognostically significant, remains debatable. Aim: to evaluate the optimal cut-off level for CD38 antigen in primary untreated CLL patients for the prognosis of disease and its association with the mutational status of immunoglobulin heavy chain genes (IGHV genes). Objects and methods: flow cytometric and molecular-genetic analysis (mutational status of IGHV genes using polymerase chain reaction followed by direct sequencing) were performed in the groups of 106 primary previously untreated CLL patients. Time-to-treatment, progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox regression. Results: The prognostic value of cut-off level CD38 antigen expression ≥ 20% or ≥ 30% does not differ significantly. Lowering of cut-off level to 7% or 5% was unsignificant. The specificity of the evaluation of the mutational status of IGHV genes based on CD38 antigen expression was low, since CD38 expression in almost half of CLL cases with unmutated IGHV genes not differ from CLL cases with mutated IGHV genes. Conclusion: the obtained data confirmed the prognostic value of CD38 antigen expression in patients at the initial stages of disease (A0-AI), primarily for assessing the duration of overall survival.
AIM:The IGHV mutational status is one of the most important markers for chronic lymphocytic leukemia (CLL) prognostication. Lipoprotein lipase (LPL) gene expression was found to correlate with IGHV status and was suggested as its surrogate marker. Recent data reported that LPL expression might be influenced by pivotal signalling pathways in CLL. This study aimed to assess LPL gene expression in relation to key immunogenetic and molecular markers of CLL, including IGHV mutational status, B-cell receptor (BCR) stereotypy, TP53, NOTCH1, and SF3B1 gene mutations. Materials and Methods: Expression of LPL mRNA was measured in peripheral blood mononuclear cells of 73 CLL patients by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). IGHV, NOTCH1, TP53, and SF3B1 gene mutation analysis was performed by PCR amplification and direct sequencing.RESULTS:44 of 73 (60%) CLL cases were categorized as LPL-positive based on the cut-off value established by ROC (receiver operating characteristic) curve analysis. LPL expression was significantly associated with IGHV mutation status (r = 0.684; p < 0.0001) and tended to correlate with presence of NOTCH1 gene mutations (p = 0.113). BCR stereotyped cases showed higher LPL expression values in comparison to unstereotyped cases in the LPL-positive group of patients (p = 0.041). LPL expression was associated with a shorter overall survival in the entire СLL group (median 107 vs 143, p = 0.048) as well as in Binet A patients, albeit with borderline significance (median 139 vs not reached, p = 0.086).CONCLUSION:LPL expression was found to be closely correlated with IGHV gene mutational status and overall survival, proving LPL as prognostic marker in CLL. Our results also indicate a possible relationship between aberrant expression of LPL and BCR- and NOTCH1-dependent signalling pathways.
BACKGROUND:The typical chronic lymphocytic leukemia (CLL) immunophenotype is vital for diagnosis, but the expression of some antigens varies and has prognostic value. There are data that reduced CD20 expression is associated with NOTCH1 and SF3B1 gene mutations.AIM:To determine a high-risk group of CLL patients for prediction of unfavorable NOTCH1 and SF3B1 gene mutations based on immunophenotyping of leukemic cells.MATERIALS AND METHODS:Flow cytometric and molecular-genetic analysis (mutations of NOTCH1, SF3B1, and TP53 genes using the polymerase chain reaction followed by direct sequencing) was performed in a group of 86 previously untreated CLL patients.RESULTS:The immunophenotype of leukemic cells of all examined patients met the criteria of CLL diagnosis. NOTCH1 gene mutations were found in 21 patients (24.4%), and SF3B1 gene mutations - in 7 patients (8.1%). There were no TP53 gene mutations among the examined patients. A decreased number of CD20+CD5+ cells and a downward trend in the relative index of mean fluorescence intensity (iMFI) of CD20+ cells were found in patients with NOTCH1 and SF3B1 gene mutations. Based on the iMFI level (higher and/or lower than 3.0) and the number of CD20+CD5+ cells among all B-cells (higher and/or lower than 50%), we distinguished CLL cases with low and relatively high levels of CD20 antigen expression. Using ROC analysis and the parameter of low CD20 antigen expression, we could predict the presence of NOTCH1 and SF3B1 gene mutations in 73.3 ± 0.06% of patients (p = 0.001). The risk of NOTCH1 and SF3B1 gene mutations in cases with low CD20 antigen expression was 6.96 (95% CI = 2.53-19.18; p = 0.0001). The revealed regularities were statistically significant for patients in whom the diagnosis was established in all Binet - Rai stages except A0-AI.CONCLUSION:Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.
AIM:To evaluate the effect of B. subtilis IMV B-7724 lectin on the functional activity of macrophages (Mph), natural killer (NK) cells and cytotoxic lymphocytes (CTL) of mice bearing Lewis lung carcinoma (LLC).MATERIALS AND METHODS:The studies were performed on C57Bl/6J mice; LLC was used as an experimental transplantable tumor. The lectin from B. subtilis IMV B-7724 was administered to LLC-bearing mice subcutaneously at a dose of 1 mg/kg of body weight for 10 days. The immunological testing was performed on days 14, 21, and 28 after tumor grafting. The cytotoxic activity of Mph, NK, and CTL was estimated in MTT-assay; the content of the stable metabolites of nitric oxide (NO) was measured by a standard Griess reaction; the arginase activity (Arg) was determined based on the measurement of urea.RESULTS:The administration of the B. subtilis IMV B-7724 lectin to LLC-bearing mice exerted its antitumor and antimetastatic effects partially via a significant (p < 0.05) increase of Mph and NK activities after the completion of the treatment. In the group of animals injected with lectin, the NO/Arg ratio increased significantly, indicating the prevalence of Mph with proinflammatory and antitumor properties. The cytotoxic activity of Mph exceeded the indices of untreated mice and intact control by 1.8 times and 5.3 times respectively; of NK - by 2.8 and 1.3 times respectively. The effect of treatment on the CTL activity was less pronounced.CONCLUSION:Antitumor and antimetastatic activity of the lectin from B. subtilis IMV B-7724 ensured the preservation of the cytotoxic activity of the main effectors of antitumor immunity (Mph, NK, and CTL) throughout LLC growth.
BACKGROUND:Identification of epitopes recognized by leukemic B cells could provide insights into the molecular mechanisms of B cell transformation in chronic lymphocytic leukemia (CLL). The aim of this paper was to compare nucleotide sequences of immunoglobulin heavy chain variable region (IGHV) genes in CLL with known sequences directed against antigens of different origins available in public databases.MATERIALS AND METHODS:Analysis was performed in the groups of 412 unselected CLL patients with productive IGHV gene using polymerase chain reaction followed by direct sequencing.RESULTS:Homology between CLL Ig sequences and antibodies directed against autoantigens was found in 12 patients (2.9%), homology between CLL Ig sequences and antiviral antibodies - in 35 patients (8.5%). Most of these sequences belonged to stereotypical clusters. Among the sequences that have homology to antiviral antibodies, the most prevalent were cases homologous with antibodies against HIV (14 cases, 3.4%) and SARS-CoV-2 antigens (10 cases, 2.4%). None of the patients in our cohort was HIV-infected and the study was conducted before the emergence of SARS-CoV-2 virus.CONCLUSIONS:Suggestions could be made about the possible impact of past infection of SARS-CoV-2 virus on the pathogenesis of CLL. In particular, an increase in the proportion of CLL cases with the expression of some stereotyped BCR and/or an increase of CLL risk in the long-term period after SARS-CoV-2 virus infection is not excluded. This assumption needs to be verified by epidemiological data.
The aim of the study is to determine the mechanisms for the formation and progressivity of chronic diffuse liver diseases in victims of the Chornobyl Nuclear Power Plant accident with the development of a diagnosis criteria for fibrous changes in this pathology. The materials were the results of examination and treatment in the clinic of the State Institution "NRCRM of the NAMS of Ukraine" of victims of the Chornobyl Nuclear Power Plant accident, 57 of which, according to the criteria for switching on and off, were assigned to the main group. The research methods were: general clinical examination, instrumental studies (ultrasound diagnostics of abdominal organs), biochemical, medical statistics, analytical. According to the results of the study, it was proved that in the victims of the Chornobyl Nuclear Power Plant accident, the main liver pathology was non-alcoholic fatty liver disease. It has been shown that in patients affected by the Chernobyl disaster, NAFLD develops a pronounced violation of fat metabolism with a reliable decrease in cholesterol and beta-lipoproteins in cirrhosis – a sign of a long-term course of the disease, accompanied not only by the development of fibrosis, but also by a fatty rebirth of liver tissue with low cholesterol and beta-lipoproteins; this can be considered a marker of cirrhosis in the Chornobyl accident clean-up personnel with NAFLD.
Aim.The study of the effect of endogenous cannabimimetic compound -N-stearoylethanolamine (NSE) on the hepatitis C virus (HCV) reproduction.Methods.The model of the surrogate HCV is a bovine diarrhea virus; cell culture model is cells transfected with cDNA of the human HCV and molecular docking has been used.Results.In vitro studies showed that NSE effectively inhibited the reproduction of a surrogate HCV in both MDBK cells and transfected Jurkat cells.Molecular docking suggested that NSE can bind to the active centers of both NS3 serine protease and HCV NS5B-polymerase and has an inhibitory effect on their activity.Conclusions.The obtained data confirm that using NSE is promising for the development of antiviral drug to suppress the HCV activity.
BACKGROUND:Expression of lipoprotein lipase (LPL) correlates with unmutated (UM) status of the variable region of the heavy chain of immunoglobulin (IGHV) genes, but the expression level of LPL in UM chronic lymphocytic leukemia (CLL) cases varies significantly.AIM:To study the association of LPL expression with the genetic variants of the TP53 gene since both genes are involved in lipid metabolism.MATERIALS AND METHODS:Expression of LPL mRNA was measured in peripheral blood mononuclears of 45 CLL patients with UM IGHV genes by real-time quantitative reverse transcription polymerase chain reaction. Mutational status of IGHV genes and TP53 genotyping (rs1042522, rs1642785, rs17883323, rs2909430, rs145153611, rs113530090, rs12947788, rs12951053, and rs17878362) were performed by polymerase chain reaction amplification followed by direct sequencing.RESULTS:Observed CLL patients were divided on groups with low (11.17 ± 2.66) and high (275.48 ± 39.37) LPL expression. In CLL patients with UM IGHV genes and low LPL expression we found an increased frequency of rs1042522 G (p = 0.0036), rs1642785 C (p = 0.0001), and rs17878362A2 alleles (p = 0.0091). The possible functional significance of these changes is discussed.CONCLUSION:Some polymorphic variants of TP53 may be genetic modifiers for LPL expression level in CLL leukemic B-cells. Further research is required in a larger cohort to confirm these findings.
Summary. Some clinical and biological features indicating an unfavorable course of the disease were found in ionizing radiation (IR) — related chronic lymphocytic leukemia (CLL) patients. The MYC proto-oncogene is considered to contribute to CLL pathogenesis. Increased MYC copy number is associated with poor prognosis in CLL. Aim: To investigate the frequency of MYC gene copy number amplification in IR-exposed CLL patients and relate the findings to the MYC mRNA levels, the presence of unfavourable prognosis mutations (TP53, SF3B1, NOTCH1), and patient's outcome. Materials and Methods: The analysis of MYC copy number was carried out by real-time quantitative polymerase chain reaction (PCR) in 70 IR-exposed CLL patients. The MYC mRNA expression was measured by real-time quantitative reverse transcription PCR. Results: Increased MYC gene copy number was present in 5.7% of cases. There was a statistically significant association between increased MYC copy number and increased MYC mRNA (p < 0.014). Additionally, somatic deletion in MYC locus was found in one patient. Most of patients (80%) with detected MYC aberrations were previously untreated, suggesting that these lesions might occur early in the course of the disease. The MYC aberrations were found mutually exclusive with high risk TP53 and SF3B1 mutations, while one case was identified, where MYC amplification and NOTCH1 mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3 vs 25 months, p = 0.008) as well as reduced overall survival (60 vs 139 months). Conclusion: Our data suggest that MYC aberrations might be an early event in IR-related CLL and contribute to aggressive disease development in the absence of high risk TP53 and SF3B1 mutations.
Research activities and scientific advance achieved in 2019 at the State Institution «National Research Center forRadiation Medicine of the National Academy of Medical Sciences of Ukraine» (NRCRM) concerning medical problemsof the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaborationwith the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annualreport. The report presents the results of fundamental and applied research works of the study of radiation effectsand health effects of the Chornobyl accident.The report also shows the results of scientific-organizational and health care work, staff training.The Scientific Council meeting of NAMS approved the NRCRM Annual Report.
Research activities and scientific advance achieved in 2018 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine» (NRCRM) concerning medical problems of the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaboration with the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annual report. The report presents the results of fundamental and applied research works of the study of radiation effects and health effects of the Chornobyl accident; fulfillment of tasks of «State Social Program for Improving Safety, Occupational Health and Working Environment in 2014-2018».The report also shows the results of scientific-organizational and health care work, staff training. The NRCRM Annual Report was approved at the Scientific Council meeting of NAMS on March 21, 2019.
Обстежені 34 особи чоловічої статі, які після участі в ліквідації наслідків аварії на Чорнобильській АЕС захворіли на неалкогольну жирову хворобу печінки (НАЖХП). Стан противірусного захисту оцінювали за рівнями антитіл класів IgG та IgM у сироватці крові. У більшості хворих на НАЖХП учасників ліквідації наслідків аварії на Чорнобильській АЕС виявлені антитіла класу IgG, але не IgM до персистуючої мікст-інфекції вірусами простого герпесу 1-го та 2-го типів, цитомегалії та вірусу Епштейна — Барр. Виявлено наявність позитивного кореляційного зв’язку між титрами антитіл до вірусів простого герпесу 1-го та 2-го типів і цитомегаловірусу (rs = 0,383, р = 0,040), а також між титрами антитіл до ядерного антигена вірусу Епштейна — Барр та антитіл до корового антигена вірусу Епштейна — Барр (rs = 0,584, р = 0,002) у хворих з персистуючою мікст-інфекцією цих герпесвірусів.
OBJECTIVE:to analyze TP53, NOTCH1 and SF3B1 mutations in chronic lymphocytic leukemia (CLL) patients, sufferersof Chornobyl NPP accident to clarify the possible relationship between ionizing radiation (IR) and CLL.METHODS:Mutations of TP53, NOTCH1, and SF3B1 genes were studied by direct sequencing in the main group of 106 CLLpatients exposed to IR due to Chornobyl NPP accident and in the control group of 130 IR non-exposed CLL patients.RESULTS:We found TP53 and SF3B1 mutations with similar incidence in both groups - 11.3 % and 10.0 % in the maingroup, and 12.7 % and 11.5 % in the control group, respectively. In contrast, the frequency of NOTCH1 mutationswas lower in IR-exposed patients (6.7 % vs 17.7 %; p = 0.012). TP53 mutations were seen with equal frequency amongmutated (11.1 %) and unmutated (11.8 %) immunoglobulin heavy-chain variable gene (IGHV) cases in IR-exposedCLL patients, while the tendency to prevalence of TP53 mutations in unmutated compared with mutated IGHV caseswas found in the control group (14.1 % and 5.6 %, correspondingly; p = 0.178). In IR-exposed group SF3B1 muta-tions were combined with mutations in TP53 almost in half of detected cases. In opposite, in the control group therewas mutual exclusivity between SF3B1 and TP53 lesions (p = 0.001). Among IR-exposed CLL patients we found two dif-ferent cases with identical rare mutation of TP53 gene - c.665C>T substitution (Pro222Leu). This substitution is verylikely to represent inherited TP53 mutation, which may influence CLL development under IR exposure.CONCLUSION:Our preliminary data suggest that TP53 abnormalities are involved in CLL development in subjectsexposed at the Chornobyl accident and also a possible connection between inherited sensitivity to ionizing radia-tion caused by mutation in TP53, radiation and CLL development.
Background: Telomeres are nucleoprotein "caps" formed of repetitive DNA sequences and specialized proteins that protect chromosomes from deterioration and fusion during mitosis.A limited number of studies have investigated the association between dietary antioxidants and leucocyte telomere length (TL).Purpose: Therefore we aimed to examine the association between plasma concentrations of antioxidants and TL in U.S adults.Methods: Participants of the National Health and Nutrition Examination Survey (NHANES) with data available on TL measures from 2001 to 2002 were included.Analyses were restricted to participants aged 18 and older.Plasma vitamins A and E, two retinyl esters, and six carotenoids were measured using high performance liquid chromatography with photodiode array detection.We used multivariable-adjusted linear regression models, accounting for the survey design and sample weights.Results: Of the 5992 eligible participants, 47.5% (n=2844) were men.The mean age was 46.9 years overall, 47.2 years in men and 46.6 in women (p=0.071).Whites (non-Hispanic) represented 50.6% (n=3031) of the participants, African-Americans 19.8% (n=1185) and Mexican-Americans 21.7% (n=1301).The mean α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, combined lutein/zeaxanthin, trans-lycopene, and retinol levels increased as TL increased (p<0.001 for all).Based on the multivariate linear regression analysis, which was performed to determine the association between adjusted level of the TL (age-sex-race-education-marital status-BMI-smoking-CRP) and antioxidants, we have found that α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin and combined lutein/zeaxanthin are positively associated telomere-to-single (T/S) ratio (for all p<0.001 for all).Conclusions: Our findings support a positive association between plasma concentrations of antioxidant and TL.This potential protective role of high antioxidant foods on TL may have important clinical implications with respect to biological aging.Further work is needed to confirm our findings, and to test whether changes in dietary antioxidants would preserve TL over time.
OBJECTIVE:This study consisted in examination the features of structural and functional state of the cardiovascular system in emergency workers (EW) of the Chernobyl nuclear power plant (ChNPP) who suffered from coronary heart disease (CHD) and having different genotypes due to polymorphism rs966221 phosphodiesterase 4D (PDE4D) gene.MATERIALS AND METHODS:The study involved 121 EW and 63 non irradiated patients with CHD. Standardized survey included echo doppler cardiography (EchoCG) that was done by Diagnostic Ultrasound System DS N3 (Mindray). Polymorphism rs966221 PDE4D determined by polymerase chain reaction followed by restriction reaction products.RESULTS:The distribution of genotypes PDE4D in EW was as follows: CC - 42, CT - 49 and TT - 30 patients. In the con trol group, carriers of the same genotypes were 27, 21 and 15 persons respectively. All echocardiographic parame ters in EW workers and non irradiated patients did not differ significantly. Amongst TT genotype carriers of both groups the proportion of patients with increased myocardial mass index was the highest (82.9%) compared to CC genotype (78.4%) and CT (71.4%). The concentric type of left ventricular (LV) hypertrophy was found in 54.9% of patients with CC genotype, in 51.8% with CT genotype and 45.7% with TT genotype, while the eccentric type in 23.5, 21.4 and 37.1% respectively. The relative number of people with high LV end diastolic volume (EDV) normalized by body surface area (BSA) was 27.5% in CC genotype carriers, 26.8% in CT genotype and 40% in TT genotype carriers (p > 0.05). The increase of BSA indexed LV end systolic volume (ESV) was found in 27.5, 30.4 and 28.6%, and the ejection fraction in 15.7, 23.2 and 22.9% respectively. The largest number of CHD patients with inadequate dias tolic function was in carriers of TT genotype (75%) compared with the data in CC (66.7%) and CT genotypes (42.9%) carriers.CONCLUSIONS:In patients with the same genotype, both EW and non irradiated persons there were virtually no dif ferences in indicators of the structural and functional status of LV. The analysis of changes of LV structure the fol lowing feature was revealed: eccentric type of LV hypertrophy was more common for patients with TT genotype, but concentric type for CC genotype carriers. In one third of patients with CC and CT genotypes and in 40% of TT geno type carriers it was observed LV systolic function disorders. Diastolic dysfunction manifested as often in patients with TT genotype compared with CC and CT genotypes carriers.