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Objective: The primary objective is to study the impact of gut microbiota and their interactions with diverse immunological markers on the development of rheumatoid arthritis. Methods: This study was performed in Astana, Kazakhstan, and included 77 Kazakh female patients older than 18 years, who met the American College of Rheumatology 2010 classification criteria for rheumatoid arthritis (RA), and 113 healthy controls. The DNA was extracted from fecal samples obtained from all study participants for subsequent sequencing at the 16S rRNA gene V1-V3 locus, facilitating the analysis of the gut microbiome. The Multiplex immunoassay was employed to measure the concentrations of inflammatory cytokines, chemokines, and immunoglobulins in both fecal and plasma samples. Results: Our taxonomic analysis revealed significant differences in the composition of the gut microbiota between the healthy control cohort and the cohort with rheumatoid arthritis RA. Alpha diversity was significantly lower in the RA group. Lachnospiraceae were the most abundant taxon and found to be crucial, showing correlations with immunological markers such as IL5. Additionally, Lachnospiraceae and Oscillospiraceae exhibited the most predictable power and distinguished the composition of both study groups. Conclusion: Our study identifies key differences in the gut microbiome of RA patients, revealing distinct microbial patterns and specific taxa abundance. We highlight potential biomarkers in immunological and bacterial pathways, offering insights into RA development and indicating possibilities for personalized treatment.
Subject(s)
Arthritis, Rheumatoid , Feces , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Humans , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/microbiology , Gastrointestinal Microbiome/immunology , Female , Middle Aged , Adult , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Case-Control Studies , Kazakhstan , Biomarkers/blood , Cytokines/metabolism , Cytokines/genetics , Cytokines/immunology , Cytokines/bloodABSTRACT
The purpose of this study was to systematise scientific publications on the combined effect of gamma radiation and heavy metals on living organisms. For this purpose, the method of analysis was applied, by means of which scientific papers in PubMed, Google Scholar, and other related databases were analysed for compliance with the inclusion criteria, where the objects of research were toxic effects of radiation and heavy metals on cells and adaptation processes. The results revealed that the study of the problem was carried out on organisms such as microalgae, fungi, weed and agricultural plants, fish, laboratory rats, and human cell cultures. In most studies, an antagonistic effect between low doses of gamma radiation and heavy metal salts was reported, which was manifested by a reduction in the cytotoxicity of isolated exposure to each agent separately. However, there are studies showing additive effects, especially in heavy metals. At the molecular level, heavy metal accumulation in combination with low doses of radiation (typically defined as less than 0.1 Gy or sievert) induces the expression of metallothionein proteins, which can bind free radicals. At the metabolic level, this is manifested by a decrease in lipid peroxidation products, activation of antioxidant enzymes, and a decrease in apoptosis. The study proved both a direct relationship between zinc and cadmium accumulation in cells and inhibition of caspases and an indirect one, by maintaining mitochondrial membrane integrity through metallothionein.
ABSTRACT
[This corrects the article DOI: 10.25122/jml-2021-0060.].
ABSTRACT
We studied the effect of the combined action of ionizing radiation and induced immobilization stress on the lipid peroxidation process and antioxidant protection of organs (mesenteric lymph nodes, spleen, adrenal glands, thymus, and liver) and immune cels - the blood lymphocytes. Results were obtained on the role of free-radical oxidation in combination with exposure to ionizing radiation and immobilization stress at an early stage in the experiment. Gamma radiation in the acute period resulted in significant changes in lipoperoxidation and antioxidant systems. The first period of immobilization stress was marked by the imbalance of LPO-AOS systems disturbance with an accumulation of toxic compounds in tissues which had affected their function. The combined sublethal gamma radiation and immobilization stress disturbed the functional activity of adaptive systems of the body in the early stage of adaptation syndrome. Furthermore, the results show the dominant role of ionizing radiation in it.
Subject(s)
Antioxidants , Oxidative Stress , Antioxidants/metabolism , Catalase/metabolism , Glutathione Peroxidase/metabolism , Humans , Lipid Peroxidation , Liver , Oxidation-Reduction , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Asbestos-related diseases are a group of diseases resulting from the inhalation of asbestos fibres and their subsequent deposition in the lung parenchyma, which causes the development of inflammatory and fibrotic processes in the respiratory system. Cases of the disease often occur in the practice of doctors. AIMS: The purpose of the study was to examine the level of circulating-free mitochondrial DNA (cf mtDNA), pro-inflammatory cytokines, immunological status and structural changes in the lung of rats exposed to various doses of asbestos dust. METHODS: Immune monitoring was performed using the peripheral blood samples of 40 male Wistar rats exposed and unexposed to asbestos dust. cf mtDNA copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were determined using a rat Enzyme Linked Immuno Sorbent Assay (ELISA) kit. RESULTS: A comprehensive assessment of the histopathological study performed under exposure to asbestos at a dose of 25 mg and 50 mg showed the presence of pronounced structural defects in the lung tissue of laboratory rats. The level of cf mtDNA in plasma of rats exposed to asbestos at a dose of 25 mg was reliably higher than that of control rats, and animals exposed to asbestos at a dose of 50 mg. The highest levels of pro-inflammatory cytokines IL-6 and TNF-a were also observed after asbestos dusting at a dose of 25 mg. CONCLUSIONS: According to the results of the immunological status obtained, the decrease in the levels of pro-inflammatory cytokines in the blood plasma at 50 mg is due to the immunosuppressive effect in the rat immune system at this dose. A positive correlation was found between TNF-a level and copy numbers of cf mtDNA at a dose of 25 mg.
Subject(s)
Asbestos , Interleukin-6 , Animals , Asbestos/toxicity , Cytokines/genetics , DNA, Mitochondrial/genetics , Dust , Interleukin-6/pharmacology , Lung , Male , Rats , Rats, WistarABSTRACT
The purposes of this study were to research immune system changes and liver and lung tissues in irradiated rats after prolonged exposure to coal dust. A study was carried out on 30 male Wistar rats that were divided into 3 groups: group I, intact animals; group II, exposure to coal dust and 0.2 Gy γ-irradiation; and group III, combined exposure to 6 Gy γ-irradiation and coal dust. The combination of a low and sublethal dose of γ-irradiation with coal dust leads to a significant change in immunity at the remote period. Particularly, the increase in radioactivity at the combined effect causes weakening of phagocytosis, and reduction in T lymphocytes by a factor of 2, immunoglobulin imbalance, and cytokine dysfunction develop secondary immune failure. During prolonged inhalation with coal dust of irradiated animals with the dose of 0.2 Gy, fibrosis and perivascular sclerosis of the bronchial wall of the lungs are formed, and perivascular fibrosis is formed in the liver. The increase in exposure dose up to 6 Gy in combination with coal, in the distant period, caused pulmonary hypertension amid hypertrophy of light arterial vessels and fibrous changes in arteriole, and destructive changes and collection necrosis develop in liver parenchyma. In the case of dust radiation synergy, the increase in doses leads to a significant immune deficiency, which occurs according to the "dose effect" principle; increases damage to animal tissues; and leads to liver tissue necrosis, pulmonary fibrosis, and pulmonary hypertension.
Subject(s)
Coal , Gamma Rays/adverse effects , Inhalation Exposure/adverse effects , Particulate Matter/toxicity , Animals , Liver/drug effects , Liver/radiation effects , Lung/drug effects , Lung/radiation effects , Male , Rats , Rats, Wistar , T-Lymphocytes/drug effects , T-Lymphocytes/radiation effectsABSTRACT
Background: Under physiological conditions, the activity of the formation of active oxygen is low. The activity of these processes is intensified under stress-induced situations. This study aimed to investigate the role of free-radical oxidation (FRO) in adrenal tissues and immunocompetent organs and cells in mature white rats after 6 hours of immobilization stress. Methods: The studies were performed on 40 White male rats of the Wistar line with a bodyweight of 200 to 240 g. Two series of experiments were conducted: I series: determination of indices in intact rats (10 rats); II series: determination of indices after a 6-hour immobilization stress action on them. Animals of II series were divided into 3 groups of 10 rats in each: group 1: those undergoing acute immobilization stress, withdrawal from the experiment in 1 hour; group 2: those undergoing acute immobilization stress, withdrawal from the experiment in 25 hours; and group 3: those undergoing acute immobilization stress, withdrawal from the experiment in 49 hours. The obtained data were processed by statistical methods with the help of the "Biostat" and "Excel" software packages. Results: In groups 1, 2, and 3, the animals were simulated acute immobilization stress by fixing the animals for 6 hours in bright light. The results of the conducted studies indicate changes in lipid peroxidation and antioxidant system (LPO-AOS) in case of immobilization stress-excitation. In developing free-radical pathology at immobilization stress-excitation, the more expressed disturbance of LPO-AOS, and accordingly the intensity of lipoperoxidation in the structural membrane of all investigated organs was high at the initial stage of exposure. Conclusion: At 49 hours after immobilization, stress less pronounced influence on the lipoperoxidation process was noted. The increase in the intensity of excessive lipoperoxidation testifies to the inhibited manifestation of AOS in the organism.
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MicroRNAs are a class of small noncoding endogenous RNAs 19-25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.