Abstract
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.
Here we report a pilot-sized study to compare the taxonomic composition of sputum microbiome in 17 newly-diagnosed lung cancer (LC) patients and 17 controls. Another object was to compare the ...representation of individual bacterial genera and species in sputum with the frequency of chromosomal aberrations in the blood lymphocytes of LC patients and in controls. Both groups were male; average age 56.1 ± 11.5 in patients and 55.7 ± 4.1 in controls. Differences in the species composition of bacterial communities in LC patients and controls were significant (pseudo-F = 1.94; p = 0.005). Increased prevalence in LC patients was detected for the genera Haemophilus and Bergeyella; whereas a decrease was observed for the genera Atopobium, Stomatobaculum, Treponema and Porphyromonas. Donors with high frequencies of chromosomal aberrations had a significant reduction in the microbiome of representatives of the genus Atopobium in the microbiome and a simultaneous increase in representatives of the species Alloprevotella compared to donors with a low level of chromosomal aberrations in lymphocytes. Thus, a comparison of the bacterial composition in the sputum of donors with cytogenetic damages in theirs lymphocytes, warrants further investigations on the potential role of microorganisms in the process of mutagenesis in somatic cells of the host body.
Fluorides are thought to be a major cause of osteocarcinogenesis, due to their widespread industrial use, ability to accumulate in bone tissue, and genotoxic and probable carcinogenic properties. In ...vitro experiments investigating the genotoxic potential of fluorides in bone tissue models can provide valuable indirect information on their involvement in osteocarcinogenesis. Here, we investigated whether sodium fluoride (NaF) has the ability to induce DNA damage and chromosomal abnormalities in human osteosarcoma cells after 48 and 72 h of exposure. The cell cultures were treated with NaF in concentrations of 0, 20, 100 and 200 μg/ml. The level of DNA damage was assessed by the comet assay, and the frequency of chromosomal abnormalities by a micronucleus test. A significant increase in DNA damage indicators was noted in the samples treated with fluoride concentrations of 100 and 200 µg/ml, after 48 and 72 h of exposure. The micronucleus test revealed a dose-dependent increase in cells with micronuclei, nucleoplasmic bridges and nuclear protrusions. Increasing the concentration of NaF led to an increase in the prevalence of cytogenetic indicators after both treatment durations. This demonstrated ability of fluorine to exert genotoxic effects on bone cells indirectly indicates the possible importance of fluoride in the aetiology of osteosarcoma.
Quantifying human genome parameters in aging Volobaev, V. P.; Kunizheva, S. S.; Uralsky, L. I. ...
Vavilovskiĭ zhurnal genetiki i selekt͡s︡ii,
09/2023, Letnik:
27, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. ...Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships.
Coal worker’s pneumoconiosis (CWP) is an occupationally induced progressive fibrotic lung disease. This irreversible but preventable disease currently affects millions across the world, mainly in ...countries with developed coal mining industries. Here, we report a pilot study that explores the sputum microbiome as a potential non-invasive bacterial biomarker of CWP status. Sputum samples were collected from 35 former and active coal miners diagnosed with CWP and 35 healthy controls. Sequencing of bacterial 16S rRNA genes was used to study the taxonomic composition of the respiratory microbiome. There was no difference in alpha diversity between CWP and controls. The structure of bacterial communities in sputum samples (β diversity) differed significantly between cases and controls (pseudo-F = 3.61; p = 0.004). A significant increase in the abundance of Streptococcus (25.12 ± 11.37 vs. 16.85 ± 11.35%; p = 0.0003) was detected in samples from CWP subjects as compared to controls. The increased representation of Streptococcus in sputum from CWP patients was associated only with the presence of occupational pulmonary fibrosis, but did not depend on age, and did not differ between former and current miners. The study shows, for the first time, that the sputum microbiota of CWP subjects differs from that of controls. The results of our present exploratory study warrant further investigations on a larger cohort.
Aging is a natural process of extinction of the body and the main aspect that determines the life expectancy for individuals who have survived to the post-reproductive period. The process of aging is ...accompanied by certain physiological, immune, and metabolic changes in the body, as well as the development of age-related diseases. The contribution of genetic factors to human life expectancy is estimated at about 25–30%. Despite the success in identifying genes and metabolic pathways that may be involved in the life extension process in model organisms, the key question remains to what extent these data can be extrapolated to humans, for example, because of the complexity of its biological and sociocultural systems, as well as possible species differences in life expectancy and causes of mortality. New molecular genetic methods have significantly expanded the possibilities for searching for genetic factors of human life expectancy and identifying metabolic pathways of aging, the interaction of genes and transcription factors, the regulation of gene expression at the level of transcription, and epigenetic modifications. The review presents the latest research and current strategies for studying the genetic basis of human aging and longevity: the study of individual candidate genes in genetic population studies, variations identified by the GWAS method, immunogenetic differences in aging, and genomic studies to identify factors of “healthy aging.” Understanding the mechanisms of the interaction between factors affecting the life expectancy and the possibility of their regulation can become the basis for developing comprehensive measures to achieve healthy longevity.
Despite the great efforts of basic and clinical research on lung cancer (LC), the prevention and treatment of this type of cancer show still far from satisfactory indicators. The complex mechanisms ...of the LC biology are already recognized, but there is a significant gap in the knowledge about the interaction of key biomarkers in the etiology and progression of this disease. The present work is aimed at studying the relationship between the telomere length (TL) and frequencies of chromosomal aberrations (CA) and micronuclei (MN) in leukocytes of primary lung cancer patients. In 67 men with lung cancer and 77 control donors (men), the baseline frequencies of CA and MN were determined in blood leukocytes, and TL was also studied. As a result, a significant increase in TL was found in lung cancer patients compared with control donors (25.86 ± 2.13 versus 15.29 ± 1.22, respectively,
p
= 0.00001). In leukocytes of LC patients, a significant increase in the baseline level of structural aberrations of chromosomes, as well as micronuclei containing centromeres, was noted. Only in the sample of lung cancer patients were direct correlations of TL with the frequency of chromosomal type aberrations and with the frequency of paired fragments revealed. In the same sample, significant inverse correlations of TL with the frequency of binucleated leukocytes containing nuclear protrusions and with the frequency of cells entering apoptosis were recorded. The study first showed that an increase in TL in lung cancer patients is associated with structural chromosomal damages, but not with the incidence of aneuploidies.
The genotoxic influence of anthracosilicosis (AC) and chronic dust bronchitis (CDB) on coal miners has been studied. Venous blood samples has been extracted from 90 coal miners with various ...occupational pulmonary diseases and 26 healthy coal miners (control group 2). Blood samples obtained from 124 non-exposed men were used as control group 1. We have found a significant increase in the frequency of the chromatid- and chromosome-type aberrations in coal miners and an increase of the chromosomal interchange in miners with occupational pulmonary diseases. The effects of the
XpD
and
XpG
genes on the level of chromosome aberrations, as well as the effect of the
XpG
gene on occupational pulmonary diseases, were discovered.
Background: Recent findings indicate that the host microbiome can have a significant impact on the development of lung cancer by inducing an inflammatory response, causing dysbiosis, and generating ...genome damage. The aim of this study was to search for bacterial communities specifically associated with squamous cell carcinoma (LUSC). Methods: In this study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with that of 40 healthy controls. Next-Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. Results: There were no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.53; p = 0.005). Genera of Streptococcus, Bacillus, Gemella, and Haemophilus were found to be significantly enriched in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. Conclusions: Among other candidates, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption.
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