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We performed a comparative study of the effects of X-ray irradiation and bleomycin on the mRNA levels of E-cadherin and tight junction proteins (claudin-3, claudin-4, claudin-18, ZO-2, and occludin) in an alveolar epithelial cell line L2. Irradiation decreased claudin-4 levels and increased occludin levels, while the levels of other mRNAs remained unchanged. Bleomycin increased the expression levels of all proteins examined except claudin-3. Irradiation and bleomycin have different effects on the expression level of intercellular junction proteins, indicating different reactions triggered in alveolar epithelial cells and a great prospects of further comparative studies.
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Células Epiteliais Alveolares , Junções Íntimas , Células Epiteliais Alveolares/metabolismo , Junções Íntimas/metabolismo , Ocludina/genética , Ocludina/metabolismo , Claudina-4/metabolismo , Claudina-3/metabolismo , Bleomicina/farmacologia , Bleomicina/metabolismo , Junções Intercelulares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Células EpiteliaisRESUMO
Perovskite-type La0.5Sr0.5Fe0.9Mo0.1O3-δ synthesized via glycine nitrate combustion and sintered at 1350 °C was found to have an orthorhombic lattice, which transforms upon heating into a rhombohedral and then a cubic one. The oxygen content and electrical conductivity in this oxide were measured in the range of oxygen partial pressures from 10-20 to 0.5 atm at 750-950 °C by coulometric titration and four-probe dc techniques, respectively. The oxygen content data were used to model the defect equilibrium in the oxide. Oxidation, charge disproportionation and electron exchange reactions between iron and molybdenum were assumed by the model to be involved in the formation of defects. The experimental data were well approximated with the model and the concentrations of charge carriers in La0.5Sr0.5Fe0.9Mo0.1O3-δ were determined to be used for the electrical conductivity analysis. The average mobility of oxygen ions and n- and p-type charge carriers was determined to be about 10-5, 0.007, and 0.07 cm2 V-1 s-1 with an activation energy of 0.80 ± 0.02, 0.34 ± 0.01, and 0.23 ± 0.01 eV, respectively. Comparison with La0.5Sr0.5FeO3-δ shows that 10% Mo substitution provides a substantial increase in both the concentration and mobility of n-type carriers, which results in an almost threefold increase in electron conductivity under reducing conditions, while maintaining a high level of ionic conductivity.
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The aim of the study was to identify the features of the genetic structure of myocardial infarction (MI) susceptibility depending on age ("early MI" denoting individuals who had the first MI before the age of 60 years, and "late MI" the group of patients with the first "MI after 60 years"). A total of 355 patients were examined (n = 121 early MI and n = 234 late MI) and 285 residents of the Siberian region (as a control group). Genotyping of 58 single nucleotide variants (SNPs) was performed using mass spectrometry using the Agena (ex Sequenom) MassARRAY® System. Statistical analysis was performed using Statistica 8.0 ("StatSoft Inc.", USA), as well as the "stats" and "genetics" packages in the R environment. The regulatory potential of SNPs was evaluated using the rSNPBase online service (http://rsnp.psych.ac.cn/). eQTL loci were identified using data from the Genotype-Tissue Expression (GTEx) project (http://www.gtexportal.org/) and the Blood eQTL online service (https://genenetwork.nl/bloodeqtlbrowser/). The GG genotype of ITGA4 rs1143674, the CC genotype of CDKN2B-AS1 rs1333049, and the CC genotype of KIAA1462 rs3739998, are generally associated with MI. The AA genotype of ADAMDEC1 rs3765124 (OR = 2.03; 95% CI 1.23-3.33; p = 0.004) and the GG genotype of AQP2 rs2878771 (OR = 2.24; 95% CI 1.23-4.09; p = 0.006) are associated with the development of MI at an early age, and the TT genotype of TAS2R38 rs1726866 (OR = 1.82; 95% CI 1.11-2.89; p = 0.009) was the high-risk genotype for the late MI. Genetic variants associated with MI are regulatory SNP (rSNP) and affect the affinity of DNA binding to transcription factors, carry out post-transcriptional control of gene activity and change the level of gene expression in various tissues. Thus, early and late MI are based on both common genetic variants of ITGA4, CDKN2B-AS1, KIAA1462 genes and specific ones (ADAMDEC1 and AQP2 for early MI and TAS2R38 for late MI).
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Predisposição Genética para Doença , Infarto do Miocárdio/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Age-related dysfunctions are accompanied by impairments in the mitochondrial morphology, activity of signaling pathway, and protein interactions. Cardiolipin is one of the most important phospholipids that maintains the curvature of the cristae and facilitates assembly and interaction of complexes and supercomplexes of the mitochondrial respiratory chain. The fatty acid composition of cardiolipin influences the biophysical properties of the membrane and, therefore, is crucial for the mitochondrial bioenergetics. The presence of unsaturated fatty acids in cardiolipin is the reason of its susceptibility to oxidative damage. Damaged cardiolipin undergoes remodeling by phospholipases, acyltransferases, and transacylases, creating a highly specific fatty acyl profile for each tissue. In this review, we discuss the variability of cardiolipin fatty acid composition in various species and different tissues of the same species, both in the norm and at various pathologies (e.g., age-related diseases, oxidative and traumatic stresses, knockouts/knockdowns of enzymes of the cardiolipin synthesis pathway). Progressive pathologies, including age-related ones, are accompanied by cardiolipin depletion and decrease in the efficiency of its remodeling, as well as the activation of an alternative way of pathological remodeling, which causes replacement of cardiolipin fatty acids with polyunsaturated ones (e.g., arachidonic or docosahexaenoic acids). Drugs or special diet can contribute to the partial restoration of the cardiolipin acyl profile to the one rich in fatty acids characteristic of an intact organ or tissue, thereby correcting the consequences of pathological or insufficient cardiolipin remodeling. In this regard, an urgent task of biomedicine is to study the mechanism of action of mitochondria-targeted antioxidants effective in the treatment of age-related pathologies and capable of accumulating not only in vitro, but also in vivo in the cardiolipin-enriched membrane fragments.
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Envelhecimento/patologia , Cardiolipinas/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismoRESUMO
INTRODUCTION: Benign prostatic hyperplasia (BPH) is one of the most common diseases in men over 50 years. The prevalence of the BPH increases with age, and pathologic features of BPH are found in about 90% of men over 80 years. AIM: The aim of the study was to study the efficacy and safety of Afalaza for the treatment of lower urinary tract symptoms (LUTS) in treatment-nave patients with BPH. MATERIALS AND METHODS: A multicenter study of using Afalaza for the treatment of LUTS in treatment-nave patients with BPH was carried out in 9 urological centers in Moscow. A total of 80 treatment-nave patients with BPH were enrolled. The improvement in the total score of IPSS, IIEF-5 and QoL after 30 weeks of therapy was evaluated as well as changes in prostate volume and maximum urinary flow rate (Qmax). RESULTS: After 30 weeks of therapy, there was a significant decrease in the total IPSS score. A decrease in the total IPSS score by 5.5 points (+37.9%) from 14.5+/-4.0 at the baseline to 9.0+/-4.1 at the visit 9 was seen. The QoL decreased by 1.8 (-38.3%) points from 4.7+/-1.0 at the baseline. The Qmax also changed from 12.7+/-4.6 to 16.4+/-5.7 (+28.3%) after 30 weeks of therapy. At the visit 9, the total IIEF5 score increased by 3.4+/-4.4 (+19.9%) from 17.1+/-4.3 at the baseline. In addition, prostate volume decreased from 42.7+/-11.1 at baseline to 41.0+/-9.8 cc post-treatment (-5.15%). A reduction of post-void residual urine volume from 26.0+/-25.3 at baseline to 17.7+/-24.2 (-31.9%) post-treatment was also shown. CONCLUSION: The results of a multicenter study demonstrate the efficacy of Afalaza for treatment of treatment-nave patients with LUTS/BPH. Afalaza reduces prostate volume and improves an erectile function.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Masculino , Moscou , Ereção Peniana/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológicoRESUMO
There are two points of view on the evolution of aging. The classical theory of aging suggests that natural selection does not efficiently eliminate mutations or alleles that are harmful to organisms at later age. Another hypothesis is that the genetic program of aging has evolved as an adaptation that contributes to the optimization of the evolutionary process. Academician V. P. Skulachev advocates the latter hypothesis, which he has illustrated with the "Fable of hares". In this paper, we have used computer simulation to search for conditions when, according to the "Fable", aging develops as an adaptation required for the evolution of useful traits. The simulation has shown that the evolutionary mechanism presented in the "Fable of hares" is only partially functional. We have found that under certain conditions, programmed deterioration of some organismal functions makes it possible to increase the efficiency of natural selection of other functions. However, we have not identified mechanisms that would ensure the distribution and support of genes of aging within the population.
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Envelhecimento/fisiologia , Simulação por Computador , Evolução Molecular , Seleção Genética , Adaptação Fisiológica , Envelhecimento/genética , Genótipo , Inteligência/genética , Mutagênese , FenótipoRESUMO
Social insects with identical genotype that form castes with radically different lifespans are a promising model system for studying the mechanisms underlying longevity. The main direction of progressive evolution of social insects, in particular, ants, is the development of the social way of life inextricably linked with the increase in the colony size. Only in a large colony, it is possible to have a developed polyethism, create large food reserves, and actively regulate the nest microclimate. The lifespan of ants hugely varies among genetically similar queens, workers (unproductive females), and males. The main advantage of studies on insects is the determinism of ontogenetic processes, with a single genome leading to completely different lifespans in different castes. This high degree of determinacy is precisely the reason why some researchers (incorrectly) call a colony of ants the "superorganism", emphasizing the fact that during the development, depending on the community needs, ants can switch their ontogenetic programs, which influences their social roles, ability to learn (i.e., the brain [mushroom-like body] plasticity), and, respectively, the spectrum of tasks performed by a given individual. It has been shown that in many types of food behavior, older ants surpass young ones in both performing the tasks and transferring the experience. The balance between the need to reduce the "cost" of non-breeding individuals (short lifespan and small size of workers) and the benefit from experienced long-lived workers possessing useful skills (large size and "non-aging") apparently determines the differences in the lifespan and aging rate of workers in different species of ants. A large spectrum of rigidly determined ontogenetic trajectories in different castes with identical genomes and the possibility of comparison between "evolutionarily advanced" and "primitive" subfamilies (e.g., Formicinae and Ponerinae) make ants an attractive object in the studies of both normal aging and effects of anti-aging drugs.
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Envelhecimento , Formigas , Comportamento Social , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Formigas/fisiologia , Humanos , Longevidade , Plasticidade NeuronalRESUMO
Due to wide spreading of inflammatory disease and imperfection of available anti-inflammatory drugs, mainly associated with their serious side effects, searching for new anti-inflammatory agents is a pressing problem. Natural triterpenoids and their synthetic analogs are a promising source of new drugs. In this study, we have investigated the anti-inflammatory and antitumor effects in vivo of the glycyrrhetinic acid derivative soloxolone methyl (SM), or methyl 2-cyano-3,12-dioxo-18ßH-olean-9(ll),l(2)-dien-30-oate. SM was shown to efficiently suppress the development of edema in a mouse model of carrageenan- or histamine-induced acute inflammation. SM also inhibited the tumor growth and reduced the tumor cell count in the ascitic fluid in mice bearing Krebs-2 carcinoma, the development of which is accompanied by an inflammatory process in the surrounding tissues.
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Carcinoma Krebs 2/tratamento farmacológico , Ácido Glicirretínico , Animais , Carcinoma Krebs 2/metabolismo , Carcinoma Krebs 2/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
OBJECTIVES: To study associations between genes of different functional classes, including fibrogenesis genes, with coronary atherosclerosis and specific features of its course. METHODS: We included in this study 404 patients with confirmed chronic ischemic heart disease (IHD) who had undergone coronary artery bypass grafting. Two groups of participants were distinguished - those with (n=188) and without (n=216) history of myocardial infarction (MI). Control group consisted of inhabitants of the Siberia region (n=285). Associations were analyzed using 48 single nucleotide polymorphisms (SNP) located in genes earlier determined as associated with diseases of the cardiovascular continuum (diabetes mellitus, MI, atherosclerosis). Multiplex genotyping was performed using mass spectrometry. For statistical analyses we used Statistica v8.0 and R-language with "stats" and "genetics" packages. RESULTS: We identified several genetic markers contributing to susceptibility to development of atherosclerosis. Same markers were identified as determinants of the character of the course of atherosclerotic disease. Risk of development of atherosclerosis was higher in carriers of the following genotypes: TT of ITGB5 gene (rs1007856) - by 1.6 times (OR=1.59; Ñ=0.0153); GG of ITGA4 gene - by 1.85 times (OR=1.85; Ñ=0.0016); GG of IGFBP7 gene (rs11133482) - by 2.4 times (OR=2.36; Ñ=0.0031). The following genotypes were identified as protective against MI and determining stable course of the disease: AA of TLR4 gene (rs4986790) (OR=0.47; Ñ=0.0104).; CC of LDLR gene (rs2738446) (OR=0,53; Ñ=0.0041); GG of OAS1 gene (rs1131454) (OR=0.50; Ñ=0.0274). CONCLUSION: Susceptibility to coronary atherosclerosis and prognosis of disease progression were found to be associated with polymorphism of certain genes, involved in metabolism of the extracellular matrix and processes of fibrogenesis (ADAMDEC1, ITGA4, ITGB5, CDKN2B-AS1, IGFBP7), lipid metabolism (LDLR), immune system functioning (TLR4, OAS1) and DNA repair (LIG1).
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Aterosclerose , Doença da Artéria Coronariana , Infarto do Miocárdio , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , SibériaRESUMO
When films are deposited from mixtures of colloidal particles of two different sizes, a diverse range of functional structures can result. One structure of particular interest is a stratified film in which the top surface layer has a composition different than in the interior. Here, we explore the conditions under which a stratified layer of small particles develops spontaneously in a colloidal film that is cast from a binary mixture of small and large polymer particles that are suspended in water. A recent model, which considers the cross-interaction between the large and small particles (Zhou et al., Phys. Rev. Lett., 2017, 118, 108002), predicts that stratification will develop from dilute binary mixtures when the particle size ratio (α), initial volume fraction of small particles (ÏS), and Péclet number are high. In experiments and Langevin dynamics simulations, we systematically vary α and ÏS in both dilute and concentrated suspensions. We find that stratified films develop when ÏS is increased, which is in agreement with the model. In dilute suspensions, there is reasonable agreement between the experiments and the Zhou et al. MODEL: In concentrated suspensions, stratification occurs in experiments only for the higher size ratio α = 7. Simulations using a high Péclet number, additionally find stratification with α = 2, when ÏS is high enough. Our results provide a quantitative understanding of the conditions under which stratified colloidal films assemble. Our research has relevance for the design of coatings with targeted optical and mechanical properties at their surface.
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In this study, we for the first time described the variability of methylation levels of 71 CpG sites in microRNA genes in leukocytes and blood vessels (coronary artery atherosclerotic plaques, intact internal thoracic arteries, and great saphenous veins) in patients with atherosclerosis using the Infinium HumanMethylation27 BeadChip microarray. Most of the analyzed CpG sites were characterized by the low variability, and most of these low-variable sites were hypomethylated in all tissue samples. CpG sites in coronary artery atherosclerotic plaques and leukocytes were similar in their methylation status. The highest variability of CpG methylation levels between different tissues was found for the CpG sites of the MIR10B gene; the methylation levels of these sites in leukocytes and atherosclerotic arteries were lower than in intact blood vessels. We also found that several cardiovascular disease risk factors, as well as medications, might affect methylation levels of CpG sites in microRNAs.
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Doença da Artéria Coronariana/metabolismo , Vasos Coronários/metabolismo , Ilhas de CpG , Metilação de DNA , Artéria Torácica Interna/metabolismo , MicroRNAs/metabolismo , Placa Aterosclerótica/metabolismo , Veia Safena/metabolismo , Doença da Artéria Coronariana/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Placa Aterosclerótica/genéticaRESUMO
Measurements of variation are of great importance for studying the stability of pathological phenomena and processes. For the biology of aging, it is very important not only to determine average mortality, but also to study its stability in time and the size of fluctuations that are indicated by the variation coefficient of lifespan (CVLS). It is believed that a relatively small (~20%) value of CVLS in humans, comparable to the coefficients of variation of other events programmed in ontogenesis (for example, menarche and menopause), indicates a relatively rigid determinism (N. S. Gavrilova et al. (2012) Biochemistry (Moscow), 77, 754-760). To assess the prevalence of this phenomenon, we studied the magnitude of CVLS, as well as the coefficients of skewness and kurtosis in diverse representatives of the animal kingdom using data provided by the Institute for Demographic Research (O. R. Jones et al. (2014) Nature, 505, 169-173). We found that, unlike humans and laboratory animals, in most examined species the values of CVLS are rather high, indicating heterogeneity of the lifespan in the cohorts studied. This is probably due to the large influence of background mortality, as well as the non-monotonicity of total mortality in the wild, especially at the earliest ages. One way to account for this influence is to "truncate" the data (removing the earliest and latest ages from consideration). To reveal the effect of this procedure, we proposed a new indicator, the stability coefficient of mortality dynamics, which indicates how quickly CVLS is reduced to values that characterize a relatively homogeneous population (33%) when the data are "truncated". Such indicators facilitate the use of the parameters of survival curves for analysis of the effects of geroprotectors, lifestyle, and other factors on lifespan, and for the quantification of relative contributions of genetic and environmental factors to the dynamics of aging in human and animal populations, including those living in the wild.
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Envelhecimento/fisiologia , Longevidade/fisiologia , Modelos Estatísticos , Animais , Evolução Biológica , Cetáceos/fisiologia , Feminino , Humanos , Masculino , Papio/fisiologiaRESUMO
Experimental adaptation of Drosophila melanogaster to nutrient-deficient starch-based (S) medium resulted in lifespan shortening, increased early-life fecundity, accelerated reproductive aging, and sexually dimorphic survival curves. The direction of all these evolutionary changes coincide with the direction of phenotypic plasticity observed in non-adapted flies cultured on S medium. High adult mortality rate caused by unfavorable growth medium apparently was the main factor of selection during the evolutionary experiment. The results are partially compatible with Williams' hypothesis, which states that increased mortality rate should result in relaxed selection against mutations that decrease fitness late in life, and thus promote the evolution of shorter lifespan and earlier reproduction. However, our results do not confirm Williams' prediction that the sex with higher mortality rate should undergo more rapid aging: lifespan shortening by S medium is more pronounced in naïve males than females, but it was female lifespan that decreased more in the course of adaptation. These data, as well as the results of testing of F1 hybrids between adapted and control lineages, are compatible with the idea that the genetic basis of longevity is different in the two sexes, and that evolutionary response to increased mortality rate depends on the degree to which the mortality is selective. Selective mortality can result in the development of longer (rather than shorter) lifespan in the course of evolution. The results also imply that antagonistic pleiotropy of alleles, which increase early-life fecundity at the cost of accelerated aging, played an important role in the evolutionary changes of females in the experimental lineage, while accumulation of deleterious mutations with late-life effects due to drift was more important in the evolution of male traits.
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Adaptação Fisiológica , Envelhecimento , Drosophila melanogaster/fisiologia , Fertilidade , Animais , Restrição Calórica , Dieta , Feminino , Longevidade , Masculino , Fenótipo , Caracteres SexuaisRESUMO
The dynamics of aging is often described by survival curves that show the proportion of individuals surviving to a given age. The shape of the survival curve reflects the dependence of mortality on age, and it varies greatly for different organisms. In a recently published paper, Stroustrup and coauthors ((2016) Nature, 530, 103-107) showed that many factors affecting the lifespan of Caenorhabditis elegans do not change the shape of the survival curve, but only stretch or compress it in time. Apparently, this means that aging is a programmed process whose trajectory is difficult to change, although it is possible to speed it up or slow it down. More research is needed to clarify whether the "rule of temporal scaling" is applicable to other organisms. A good indicator of temporal scaling is the coefficient of lifespan variation: similar values of this coefficient for two samples indicate similar shape of the survival curves. Preliminary results of experiments on adaptation of Drosophila melanogaster to unfavorable food show that temporal scalability of survival curves is sometimes present in more complex organisms, although this is not a universal rule. Both evolutionary and environmental changes sometimes affect only the average lifespan without changing the coefficient of variation (in this case, temporal scaling is present), but often both parameters (i.e. both scale and shape of the survival curve) change simultaneously. In addition to the relative stability of the coefficient of variation, another possible argument in favor of genetic determination of the aging process is relatively low variability of the time of death, which is sometimes of the same order of magnitude as the variability of timing of other ontogenetic events, such as the onset of sexual maturation.
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Envelhecimento/fisiologia , Caenorhabditis elegans/fisiologia , Modelos Biológicos , Animais , Drosophila melanogasterRESUMO
Accumulation of various types of lesions in the course of aging increases an organism's vulnerability and results in a monotonous elevation of mortality rate, irrespective of the position of a species on the evolutionary tree. Stroustrup et al. (Nature, 530, 103-107) [1] showed in 2016 that in the nematode Caenorhabditis elegans, longevity-altering factors (e.g. oxidative stress, temperature, or diet) do not change the shape of the survival curve, but either stretch or shrink it along the time axis, which the authors attributed to the existence of an "aging program". Modification of the accelerated failure time model by Stroustrup et al. uses temporal scaling as a basic approach for distinguishing between quantitative and qualitative changes in aging dynamics. Thus we analyzed data on the effects of various longevity-increasing genetic manipulations in flies, worms, and mice and used several models to choose a theory that would best fit the experimental results. The possibility to identify the moment of switch from a mortality-governing pathway to some other pathways might be useful for testing geroprotective drugs. In this work, we discuss this and other aspects of temporal scaling.
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Envelhecimento/fisiologia , Mortalidade , Animais , Humanos , Longevidade , Modelos Biológicos , Análise de SobrevidaRESUMO
A group of patients with ischemic heart disease and myocardial infarction (N = 156) and a reference population sample (N = 300) were genotyped for 58 single nucleotide polymorphisms (SNPs) in the genes involved in extracellular matrix function and collagen metabolism or associated with cardiovascular diseases and atherosclerotic plaque stability. Genotyping was performed by mass-spectrometry with two multiplex sets of 27 and 31 SNPs. The study revealed different genetic composition of predisposition to cardiovascular disease continuum (CVDC) syntropy (patients with concomitant conditions: hypercholesterolemia, hypertension, and type-II diabetes mellitus, N = 96) and to isolated myocardial infarction (without these conditions, N = 60). Only the KIAA1462 gene (rs3739998) showed associations with both CVDC syntropy (OR = 1.71; 95% CI 1.19-2.45; Ñ = 0.003) and isolated infarction (OR = 1.58; 95% CI 1.05-2.40; Ñ = 0.028). Isolated myocardial infarction was also associated with LIG1 (rs20579) (OR = 2.08; 95% CI 1.06-4.17; Ñ = 0.028) and ADAMDEC1 (rs3765124) (OR = 1.63; 95% CI 1.07-2.50; Ñ = 0.020). CVDC syntropy was associated with CDKN2BAS1 (rs1333049) (OR = 1.48; 95% CI 1.03-2.12; Ñ = 0.029) and APOA2 (rs5082) (OR = 1.47; 95% CI 1.02-2.11; Ñ = 0.035). So, genes involved in fibrogenesis contribute to predisposition to the myocardial infarction as well. Isolated myocardial infarction and CVDC syntropy can be considered as pathogenetically different cardiovascular conditions, with different genes that contribute to the susceptibility.
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Predisposição Genética para Doença , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
For identification of somatic mitochondrial DNA (mtDNA) mutations, the mtDNA major noncoding region (D-loop) sequence in blood samples and carotid atherosclerosis plaques from patients with atherosclerosis was analyzed. Five point heteroplasmic positions were observed in 4 of 23 individuals (17%). Only in two cases could heteroplasmy have resulted from somatic mutation, whereas three heteroplasmic positions were found in both vascular tissue and blood. In addition, length heteroplasmy in a polycytosine stretches was registered at nucleotide positions 303-315 in 16 individuals, and also in the 16184-16193 region--in four patients. The results suggest that somatic mtDNA mutations can occur during atherosclerosis, but some heteroplasmic mutations may appear in all tissues, possibly being inherited.
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Aterosclerose/genética , Artérias Carótidas/patologia , DNA Mitocondrial/genética , Placa Aterosclerótica/genética , Idoso , DNA Mitocondrial/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Mutação Puntual/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: Comparative study of tight junctions and ultrastructure alterations of enterocytes of mucous membranes of jejunum of rats under the effect of lipopolysaccharides and cholera toxin. MATERIALS AND METHODS: Lipopolysaccharides (Sigma-Aldrich, Germany) and cholera toxin (Sigma-Aldrich, Germany) were used. The study was carried out in Wistar line rats. Effect of lipopolysaccharides and cholera toxin on epitheliocytes was carried out by a method of withdrawal of segments of rat jejunum and their incubation with the specified substances. Comparative analysis of ultrathin sections of enterocytes of jejunum of rats and tight junctions between them was carried out in control and under the effect of lipopolysaccharides and cholera toxin. RESULTS: Effect of lipopolysaccharides on ultrastructure of enterocytes of rat jejunum manifested in the change of cell form as a result of increase of intercellular space without destruction of tight junctions. Disappearance of desmosomes, increase of nuclei and more pronounced ER were noted in some epitheliocytes. Effect of cholerogen on epitheliocytes of mucous membrane of rat jejunum by a number of signs is similar to the effect of lipopolysaccharides, that manifested in an alteration of ultrastructure of cell, the form of those also transformed as a result of an increase of intercellular space, this process was not accompanied by destruction of tight junctions. Disappearance of folding of the lateral region of plasmatic membrane of cells and a reduction of a number of microvilli was observed under the effect of cholera toxin. CONCLUSION: A similar character of effect of lipopolysaccharides and cholera toxins on ultrastructure of cells and region of tight junctions of enterocytes of rat jejunum was detected, both substances caused an increase of intercellular space without the destruction of tight junctions.
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Toxina da Cólera/farmacologia , Jejuno/ultraestrutura , Lipopolissacarídeos/farmacologia , Junções Íntimas/ultraestrutura , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Desmossomos/efeitos dos fármacos , Desmossomos/ultraestrutura , Células Epiteliais/citologia , Humanos , Jejuno/efeitos dos fármacos , Masculino , Ratos , Junções Íntimas/efeitos dos fármacosRESUMO
The data revealed by comparative embryology of the basal (diploblastic) metazoans is traditionally considered a valuable potential source of information on the origin and early evolution of the animal kingdom and its major clades. Special attention is paid to the fundamental morphogenetic process of gastrulation during which the cells of the early embryo differentiate into the germ layers and the primary body plan is formed. Comparative analysis of gastrulation in different cnidarian taxa reveals high level of intergroup, intragroup, and individual variation. With few exceptions, there is no robust correlation between the type of gastrulation and the taxon. Current data do not support the idea that morphogenetic processes underlying cnidarian gastrulation can be divided into several distinct types. Rather, there is a continuum of equifinal ontogenetic trajectories. In cnidarians, the mode of gastrulation apparently depends less on the macroevolutionary history of the species than on various evolutionary plastic features, such as the oocyte size, the amount of yolk, the number of cells at the blastula (or morula) stage, the presence of phototrophic symbionts, or the ecology of the larva. Thus, in cnidarians, morphogenetic basis of gastrulation contains only a very weak phylogenetic signal and can have only limited application in phylogenetic reconstructions. On the other hand, comparative studies of the ontogeny of the basal metazoans shed light on the general rules of the evolution of morphogenetic processes that is crucial for understanding the early history of the animal kingdom.
Assuntos
Evolução Biológica , Cnidários/crescimento & desenvolvimento , Gastrulação , Animais , Blastoderma/citologia , Blastoderma/embriologia , Blastoderma/crescimento & desenvolvimento , Diferenciação Celular , Cnidários/citologia , Cnidários/embriologia , Camadas Germinativas/citologia , Camadas Germinativas/embriologia , Camadas Germinativas/crescimento & desenvolvimento , FilogeniaRESUMO
Adaptation to stress factors is often accompanied by negative side effects that are manifested in lower fitness in the absence of the stress factor. This can lead to ecological specialization of the populations adapted to stressful environment and, ultimately, to ecological speciation. However, the existence of eurytopic species with a wide spectrum of ecological tolerance implies that adaptation to marginal conditions apparently can proceed without negative side effects or even involve positive effects, leading to niche expansion. Experimental evidence in favour of this evolutionary scenario is scarce. In the course of the evolutionary experiment that lasted for 20 generations, the laboratory populations of Drosophila melanogaster successfully adapted to stressful media with high NaCl concentration. The adaptation is manifested through the higher number of offspring produced during a fixed time interval by a pair of parents from the adapted lineages on the stressful medium compared to the control (unadapted) lineage, and in the less pronounced delay in larval development caused by high NaCl concentration. The adaptation to stressful medium did not entail fitness costs on the standard (favorable) medium; moreover, it resulted in more effective reproduction in favorable conditions (expansion of the trophic niche). These results, together with those obtained earlier during the study of adaptation of D. melanogaster to nutrient-poor starch based medium, imply that adaptation to marginal conditions accompanied by positive (rather than negative) side effects, leading to the expansion of the trophic niche, may be a frequent phenomenon in eurytopic species like D. melanogaster, probably explaining, to some extent, their ecological tolerance. Scarcity of experimentally confirmed examples of such evolutionary scenario is probably due to low number of attempts to find them. One possible mechanism of 'multi-purpose adaptations' obtained during the acclimation to environmental stress is the adaptive changes of symbiotic microbiota which, in Drosophila, is efficiently transferred between generations if offspring eat the medium on which their parents had lived. For instance, high quantities of symbiotic lactobacilli in the gut can enhance larval growth, life span of adults, and the efficiency of substrate utilization. Further studies are needed to reveal the mechanisms responsible for the changes in fitness observed in the course of the experiment.